AAPS - American Association of Pharmaceutical Scientists

AAPS - American Association of Pharmaceutical Scientists
Focus Group - Protein Aggregation and Biological Consequences
http://www.aapspharmaceutica.com/inside/focus_groups/ProteinAgg/index.asp
Dear Colleague:
The focus group steering committee, group members and, contributors are pleased to present our literature collection summary.
Our goal is to provide you with a structured reference of published information to foster focused scientific discussions in the community
around the topics of protein aggregation/particles and observations of unwanted reactions, especially immunogenicity.
This collection is build, maintained, and expanded as a strictly voluntary effort for which we also kindly ask for your knowledgeable
contributions through the literature collection portal on our website.
The collection is structured according to the primary and secondary focus topic of the references as given in the table of contents. We
hope you find this collection helpful.
Abbreviations: phys. stress: physical stress; f-t: freeze-thaw
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Table of Contents
1
2
3
4
Aggregate/Particle and molecular structure 4
1.1
Aggregate/Particle and long-term storage 5
1.2
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 5
1.3
Aggregate/Particle detection/characterization 5
1.4
Immunogenicity observation - acute and/or sporadic 10
1.5
Immunogenicity observation - chronic and/or general 10
1.6
Immunogenicity assays 10
Aggregate/Particle and long-term storage 11
2.1
Aggregate/Particle and molecular structure 11
2.2
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 11
2.3
Aggregate/Particle detection/characterization 11
2.4
Immunogenicity observation - acute and/or sporadic 11
2.5
Immunogenicity observation - chronic and/or general 11
2.6
Immunogenicity assays 11
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 12
3.1
Aggregate/Particle and molecular structure 12
3.2
Aggregate/Particle and long-term storage 13
3.3
Aggregate/Particle detection/characterization 13
3.4
Immunogenicity observation - acute and/or sporadic 22
3.5
Immunogenicity observation - chronic and/or general 22
3.6
Immunogenicity assays 22
Aggregate/Particle detection/characterization 23
4.1
Aggregate/Particle and molecular structure 31
4.2
Aggregate/Particle and long-term storage 35
Page 2 of 46
Version 30 July 2010
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
5
6
7
4.3
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 35
4.4
Immunogenicity observation - acute and/or sporadic 39
4.5
Immunogenicity observation - chronic and/or general 39
4.6
Immunogenicity assays 39
Immunogenicity observation - acute and/or sporadic 41
5.1
Aggregate/Particle and molecular structure 41
5.2
Aggregate/Particle and long-term storage 41
5.3
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 41
5.4
Aggregate/Particle detection/characterization 41
5.5
Immunogenicity observation - chronic and/or general 41
5.6
Immunogenicity assays 41
Immunogenicity observation - chronic and/or general 42
6.1
Aggregate/Particle and molecular structure 42
6.2
Aggregate/Particle and long-term storage 42
6.3
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 42
6.4
Aggregate/Particle detection/characterization 42
6.5
Immunogenicity observation - acute and/or sporadic 42
6.6
Immunogenicity assays 43
Immunogenicity assays 44
7.1
Aggregate/Particle and molecular structure 44
7.2
Aggregate/Particle and long-term storage 44
7.3
Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 44
7.4
Aggregate/Particle detection/characterization 45
7.5
Immunogenicity observation - acute and/or sporadic 45
7.6
Immunogenicity observation - chronic and/or general 45
Page 3 of 46
Version 30 July 2010
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
1 Aggregate/Particle and molecular structure
Data
Source
In vitro
in vitro
Substance
Class
Peptide
Protein
In vitro
In vitro
Protein
Further substance
classification /
Substance name
Corresponding
author / Group
head
Title
Kar
Aromatic Interactions Promote SelfAssociation of Collagen Triple-Helical
Peptides to Higher-Order Structures
Chaperonin
Apetri
Chaperonin chamber accelerates
protein folding through passive action
of preventing aggregation
Silica
Radhakrishnan
A Novel Route to Organic-Inorganic
Hybrid Nanomaterials
Collagen
sphingomyelinases D
In vitro
In vitro
Antibody
In vivo
animal
In vitro
Ig
Liposome
Protein
prion protein
Pires
Structural insights into the catalytic
mechanism of sphingomyelinases D
and evolutionary relationship to
glycerophosphodiester
phosphodiesterases
Benzyl (3-Acylaminopropyl)
Dimethylammonium Chloride
Surfactants: Structure and Some
Properties of the Micellar Aggregates
Kulahin
Expression, crystallization and
preliminary X-ray analysis of the
extracellular Ig modules I-IV and F3
modules I-III of the neural celladhesion molecule L1
Whiteman
Poly(HPMA)-coated liposomes
demonstrate prolonged circulation in
mice
Lisa
The structural intolerance of the PrP
alpha-fold for polar substitution of the
helix-3 methionines
Murakami
Page 4 of 46
Full citation
K. Kar, S. Ibrar, V. Nanda, T. M. Getz, S. P. Kunapuli, B.
Brodsky: Aromatic Interactions Promote Self-Association of
Collagen Triple-Helical Peptides to Higher-Order Structures,
Biochemistry 48(33): 7959-7968 (2009)
A. C. Apetri, A. L. Horwich: Chaperonin chamber
accelerates protein folding through passive action of
preventing aggregation, Proceedings of the National
Academy of Sciences 105(45): 17351-17355 (2008)
B. Radhakrishnan, A. N. Constable, W. J. Brittain: A Novel
Route to Organic-Inorganic Hybrid Nanomaterials,
Macromolecular Rapid Communications 29(22): 1828-1833
(2009)
M. T. Murakami, M. F. Fernandes-Pedrosa, S. A. de
Andrade, A. Gabdoulkhakov, C. Betzel, D. V. Tambourgi, R.
K. Arni: Structural insights into the catalytic mechanism of
sphingomyelinases D and evolutionary relationship to
glycerophosphodiester phosphodiesterases, Biochemical
and Biophysical Research Communications 342(1): 323329 (2006)
P. A. R. Pires, O. A. El Seoud: Benzyl (3-Acylaminopropyl)
Dimethylammonium Chloride Surfactants: Structure and
Some Properties of the Micellar Aggregates, Progress in
Colloid and Polymer Science 133: 131-141
N. Kulahin, C. Kasper, O. Kristensen, J. S. Kastrup, V.
Berezin, E. Bock, M. Gajhede: Expression, crystallization
and preliminary X-ray analysis of the extracellular Ig
modules I-IV and F3 modules I-III of the neural celladhesion molecule L1, Acta Crystallographica Section F 61:
858-860 (2005)
K. R. Whiteman, V. Subr, K. Ulbrich, V. P. Torchilin:
Poly(HPMA)-coated liposomes demonstrate prolonged
circulation in mice, Journal of Liposome Research 11(2-3):
153-164 (2001)
S. Lisa, M. Meli, G. Cabello, R. Gabizon, G. Colombo, M.
Gasset: The structural intolerance of the PrP alpha-fold for
polar substitution of the helix-3 methionines, Cellular and
Molecular Life Sciences (May 2010)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
1.1 Aggregate/Particle and long-term storage
N/A
1.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
Data Source
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
In vitro
Protein
Barstar
Kumar
Title
Structurally Distinct Amyloid
Protofibrils Form on Separate
Pathways of Aggregation of a
Small Protein
Sanchez
MDM4 binds ligands via a
mechanism in which disordered
regions become structured
In vitro
No
experimental
data
No
experimental
data
Protein
MDM4, MDM2
In vitro
Antibody
IgG1 antibody
Mahler H-C.
In vitro
Antibody
IgG1 antibody
Kiese Sylvia
In vitro
Protein
In vitro
Antibody
Protein
0 Wang W.
Protein
0 Wang W.
0 Strambini GB
antibody IgG
Hansson U.
Protein aggregation and its
inhibition in biopharmaceutics
Instability, stabilization and
formulation of liquid protein
pharmaceuticals
Induction and analysis of
aggregates in a liuqid IgG1antibody formulation
Shaken, not stirred: Mechanical
Stress testing of an IgG1 antibody
Proteins in frozen solutions:
evidence of ice-induced partial
unfolding
Aggregation of human
immunoglobulin G upon freezing
Full citation
S. Kumar, J. B. Udgaonkar: Structurally Distinct
Amyloid Protofibrils Form on Separate Pathways of
Aggregation of a Small Protein, Biochemistry 48(27):
6441-6449 (2009)
M. C. Sanchez, J. G. Renshaw, G. Davies, P. N.
Barlow, M. Vogtherr: MDM4 binds ligands via a
mechanism in which disordered regions become
structured, FEBS Letters 584(14): 3035-3041(2010)
Wang W.: Protein aggregation and its inhibition in
biopharmaceutics, Int. J .Pharm., 289: 1-30 (2005)
Wang W.: Instability, stabilization and formulation of
liquid protein pharmaceuticals, Int. J. Pharm.185: 129188; (1999)
Mahler H.-C., Müller R., Frieß W., Delille A., Matheus
S.: Induction and analysis of aggregates in a liuqid
IgG1-antibody formulation, EJPB 59: 407-417 (2005)
Kiese S., Pappenberger A., Friess W., Mahler H.-C.:
Shaken, not stirred: Mechanical Stress testing of an
IgG1 antibody, JPS: 1-20 (2007)
Strambini G. B., Gabellieri E.: Proteins in frozen
solutions: evidence of ice-induced partial unfolding,
Biophys. J. 70: 971-976 (1996)
Hansson U.: Aggregation of human immunoglobulin G
upon freezing, Acta Chem. Scand., 22:
483-489 (1968)
1.3 Aggregate/Particle detection/characterization
Data Source
Further substance
Substance classification /
Class
Substance name
Corresponding
author / Group
head
Title
Full citation
Page 5 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
N- acetyl chitosan
Hu
In vitro
Protein
alphaA-crystallin
Biswas
In vitro
Protein
alphaB-crystallin
Ecroyd
poly(1,3cyclohexadiene)
Natori
In vitro
In vitro
Pires
In vitro
Protein
alphaB-crystallin
Santhoshkumar
In vitro
Protein
betaA3-crystallin
Gupta
mRNA
Niedzwiecka
prion protein
Frankenfield
In vitro
In vitro
Protein
Version 30 July 2010
Y. Hu, Y. Du, J. Yang, Y. Tang, J. Li, X. Wang:
Self-aggregation and antibacterial activity of NSelf-aggregation and antibacterial activity of acylated chitosan, Polymer 48(11): 3098-3106
N-acylated chitosan
(2007)
A. Biswas, A. Miller, T. Oya-Ito, P.
Santhoshkumar, M. Bhat, R. H. Nagaraj: Effect of
Effect of site-directed mutagenesis of
site-directed mutagenesis of methylglyoxalmethylglyoxal-modifiable arginine residues
modifiable arginine residues on the structure and
on the structure and chaperone function of
chaperone function of human alphaA-crystallin,
human alphaA-crystallin
Biochemistry 45(14): 4569-4577 (2006)
H. Ecroyd, S. Meehan, J. Horwitz, J.A. Aquilina,
J.L.P. Benesch, C.V. Robinson, C.E. MacPhee,
J.A. Carver: Mimicking phosphorylation of alphaBcrystallin affects its chaperone activity, The
Mimicking phosphorylation of alphaBBiochemical Journal 401(1):129-141(2006)
crystallin affects its chaperone activity
I. Natori, H. Sato: Aggregation of poly(1,3cyclohexadiene): effects of molecular weight and
Aggregation of poly(1,3-cyclohexadiene):
polymer chain structure, Journal of Polymer
effects of molecular weight and polymer
Science Part B: Polymer Physics 44: 1442-1452
chain structure
(2006)
P. A. R. Pires, O. A. El Seoud: Surfactants with an
amide group "spacer": Synthesis of 3Surfactants with an amide group "spacer":
Synthesis of 3(acylaminopropyl)trimethylammonium chlorides
and their aggregation in aqueous solutions,
(acylaminopropyl)trimethylammonium
chlorides and their aggregation in aqueous
Journal of Colloid and Interface Science 304(2):
474-485
solutions
P. Santhoshkumar, K. K. Sharma: Conserved F84
and P86 residues in alphaB-crystallin are
Conserved F84 and P86 residues in alphaB- essential to effectively prevent the aggregation of
crystallin are essential to effectively prevent substrate proteins, Protein Science 15(11): 2488the aggregation of substrate proteins
2498 (2006)
R. Gupta, K. Srivastava, O. P. Srivastava:
Truncation of motifs III and IV in human lens
Truncation of motifs III and IV in human lens betaA3-crystallin destabilizes the structure,
betaA3-crystallin destabilizes the structure
Biochemistry 45(33): 9964-9978 (2006)
A. Niedzwiecka, E. Darzynkiewicz, R. Stolarski:
Deaggregation of elF4E Induced by mRNA 5' Cap
Deaggregation of elF4E Induced by mRNA
Binding, Nucleosides, Nucleotides, and Nucleic
5' Cap Binding
Acids 24(5-7): 507-511 (2005)
K. N. Frankenfield, E. T. Powers, J. W. Kelly:
Influence of the N-terminal domain on the
Influence of the N-terminal domain on the
aggregation properties of the prion protein, Protein
aggregation properties of the prion protein
Science 14: 2154-2166 (2005)
Page 6 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
Copolymers
Protein
alphaB-crystallin
Abbel
Rod-Length Dependent Aggregation in a
Series of Oligo(p-benzamide)-BlockPoly(ethylene glycol) Rod-Coil Copolymers
Aquilina
Phosphorylation of alphaB-crystallin alters
chaperone function through loss of dimeric
substructure
In vitro
Protein
alpha-crystallin
Horwitz
The native oligomeric organization of alphacrystallin, is it necessary for its chaperone
function?
In vitro
Protein
prolactin
Keeler
The tertiary structure and backbone
dynamics of human prolactin
In vitro
Protein
Alpha-crystallin
Horwitz
Alpha-crystallin
Erhardt
Amphiphilic janus micelles with polystyrene
and poly(methacrylic acid) hemispheres
Gaylor
Water-soluble conjugated oligomers: effect
of chain length and aggregation on
photoluminescence-quenching efficiencies
Aydogan
Comparison of the surface activity and bulk
aggregation of ferrocenyl surfactants with
cationic and anionic headgroups
In vitro
In vitro
In vitro
ferrocenyl surfactant
Page 7 of 46
Version 30 July 2010
R. Abbel, T. W. Schleuss, H. Frey, A. F. M.
Kilbinger: Rod-Length Dependent Aggregation in
a Series of Oligo(p-benzamide)-BlockPoly(ethylene glycol) Rod-Coil Copolymers,
Macromolecular Chemistry and Physics 206(20):
2067-2074 (2005)
J. A. Aquilina, J. L. P. Benesch, L. L. Ding, O.
Yaron, J. Horwitz, C. V. Robinson:
Phosphorylation of alphaB-crystallin alters
chaperone function through loss of dimeric
substructure, Journal of Biological Chemistry
279(27): 28675-28680 (2004)
J. Horwitz, Q. Huang, L. Ding: The native
oligomeric organization of alpha-crystallin, is it
necessary for its chaperone function?
Experimental Eye Research 79(6): 817-821
(2004)
C. Keeler, P. S. Dannies, M. E. Hodsdon: The
tertiary structure and backbone dynamics of
human prolactin, Journal of Molecular Biology
328(5): 1105-1121 (2003)
J. Horwitz: Alpha-crystallin, Experimental Eye
Research 76(2): 145-153 (2003)
R. Erhardt, M. Zhang, A. Böker, H. Zettl, C. Abetz,
P. Frederik, G. Krausch, V. Abetz, A. H. E.
Mueller: Amphiphilic janus micelles with
polystyrene and poly(methacrylic acid)
hemispheres, Journal of American Chemical
Society 125(11): 3260-3267 (2003)
B. S. Gaylord, S. Want, A. J. Heeger, G. C.
Bazan: Water-soluble conjugated oligomers: effect
of chain length and aggregation on
photoluminescence-quenching efficiencies,
Journal of the American Chemical Society 123:
6417-6418 (2001)
N. Aydogan, N. L. Abbott: Comparison of the
surface activity and bulk aggregation of ferrocenyl
surfactants with cationic and anionic headgroups,
Langmuir 17(19): 5703-5706 (2001)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
Peptid
Protein
Mong
Beta-alanine-based dendritic beta-peptides:
dendrimers possessing unusually strong
binding ability towards protic solvents and
their self-assembly into nanoscale
aggregates through hydrogen-bond
interactions
Nakasako
Tertiary and quaternary strucutres of
photoreactive Fe-type nitrile hydratase from
Rhodococcus sp. N-771: roles of hydration
water molecules in stabilizing the strucutres
and the structural origin of the substrate
specificity of the enzyme
Yu
Multiple morphologies formed from an
amphiphilic ABC triblock copolymer in
solution
Maruyama
Nanoparticle DNA carrier with Poly(L-lysine)
grafted polysaccharide copolymer and
Poly(D,L-lactic acid)
Calcitonin
Costantino
Development of Calcitonin Salmon Nasal
Spray: Similarity of Peptide Formulated in
Chlorobutanol Compared to Benzalkonium
Chloride as Preservative
Chlorhexidine
Zeng
Concentration dependent aggregation
properties of chlorhexidine salts
Walton
The cavity-chaperone Skp protects its
substrate from aggregation but allows
independent folding of substrate domains
dendritic betapeptides
hydratase
In vitro
Copolymers
In vitro
polysaccaride
copolymers
In vitro
Peptide
In vitro
In vitro
Protein
Skp
Page 8 of 46
Version 30 July 2010
T. K.-K. Mong, A. Niu, H.-F. Chow, C. Wu, L. Li, R.
Chen: Beta-alanine-based dendritic beta-peptides:
dendrimers possessing unusually strong binding
ability towards protic solvents and their selfassembly into nanoscale aggregates through
hydrogen-bond interactions, Chemistry - A
European Journal 7(3): 686-699 (2001)
M. Nakasako, M. Odaka, M. Yohda, N. Dohmae,
K. Takio, N. Kamiya, I. Endo: Tertiary and
quaternary strucutres of photoreactive Fe-type
nitrile hydratase from Rhodococcus sp. N-771:
roles of hydration water molecules in stabilizing
the strucutres and the structural origin of the
substrate specificity of the enzyme, Biochemistry
38(31): 9887-9898 (1999)
G. -E. Yu, A. Eisenberg: Multiple morphologies
formed from an amphiphilic ABC triblock
copolymer in solution 31 (16): Macromolecules:
5546–5549 (1998)
A. Maruyama, T. Ishihara, J. -S. Kim, S. W. Kim,
T. Akaike: Nanoparticle DNA carrier with Poly(Llysine) grafted polysaccharide copolymer and
Poly(D,L-lactic acid), Bioconjugate Chemistry 8
(5): 735–742 (1997)
H. R. Costantino, H. Culley, L. Chen, D. Morris, M.
Houston, S. Roth, M. J. Phoenix, C. Foerder, J. S.
Philo, T. Arakawa, L. Eidenschink, N. H.
Andersen, G. Brandt, S. C. Quay: Development of
Calcitonin Salmon Nasal Spray: Similarity of
Peptide Formulated in Chlorobutanol Compared to
Benzalkonium Chloride as Preservative, Journal of
Pharmaceutical Science 98(10):3691-3706 (2009)
P. Zeng, G. Zhang, A. Rao, W. Bowles, T. S.
Wiedmann: Concentration dependent aggregation
properties of chlorhexidine salts, International
Journal of Pharmaceutics 367(1-2): 73-78 (2009)
T. A. Walton, C. M. Sandoval, C. A. Fowler, A.
Pardi, M. C. Sousa: The cavity-chaperone Skp
protects its substrate from aggregation but allows
independent folding of substrate domains,
Proceedings of the National Academy of Sciences
106(6): 1772-1777 (2009)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
Protein
Protein
beta2-Microglobulin
Legumin
Antonov
Macromolecular complexes of the main
storage protein of Vicia faba seeds with
sulfated polysaccharide
Poly(L-glutamic acid),
Poly(Nisopropylacrylamide) He
In vitro
In vitro
In vitro
Eichner
A Generic Mechanism of beta2Microglobulin Amyloid Assembly at Neutral
pH Involving a Specific Proline Switch
Novel Temperature- and pH-Responsive
Graft Copolymers Composed of Poly(Lglutamic acid) and Poly(Nisopropylacrylamide)
Liu
Vesicular aggregation and morphologic
evolvement of a flexible-rigid block
hydrogen-bonding complex
Hwang
Interruptions in the collagen repeating
tripeptide pattern can promote
supramolecular association
Protein
Collagen
In vitro
Peptide
nucleic acidcontaining
nanoparticles
Bartlett
Physicochemical and biological
characterization of targeted, nucleic acidcontaining nanoparticles
In vitro
Protein
Ure2
Perrett
Equilibrium folding properties of the yeast
prion protein determinant Ure2
protein therapeutics
Tatford O.C.
Analytical techniques for the evaluation of
liquid protein therapeutics
No
experimental
data
Protein
Please
select
Protein
0 Fink, A.L.
Protein aggregation: folding aggregates,
inclusion bodies and amyloid
Page 9 of 46
Version 30 July 2010
T. Eichner, S. E. Radford: A Generic Mechanism
of beta2-Microglobulin Amyloid Assembly at
Neutral pH Involving a Specific Proline Switch,
Journal of Molecular Biology 386(5): 1312-1326
(2009)
Y. A. Antonov, T. Sato: Macromolecular
complexes of the main storage protein of Vicia
faba seeds with sulfated polysaccharide, Food
Hydrocolloids 23(3): 996-1006 (2009)
C. He, C. Zhao, X. Guo, Z. Guo, X. Chen, X.
Zhuang, S. Liu, X. Jing: Novel Temperature- and
pH-Responsive Graft Copolymers Composed of
Poly(L-glutamic acid) and Poly(Nisopropylacrylamide), Journal of Polymer Science,
Part A: Polymer Chemistry 46(12): 4140-4150
(2008)
Q. Liu, Y. Wang, W. Li, L. Wu: Vesicular
aggregation and morphologic evolvement of a
flexible-rigid block hydrogen-bonding complex,
Polymer 49(19): 4159-4167 (2008)
E. S. Hwang, G. Thiagarajan, A. S. Parmar, B.
Brodsky: Interruptions in the collagen repeating
tripeptide pattern can promote supramolecular
association, Protein Science 19(5): 1053-1064
(2010)
D. W. Bartlett, M. E. Davis: Physicochemical and
biological characterization of targeted, nucleic
acid-containing nanoparticles, Bioconjugate
Chemistry 18 (2): 456–468 (2007)
S. Perrett, S. J. Freeman, P. J. G. Butler, A. R.
Fersht: Equilibrium folding properties of the yeast
prion protein determinant Ure2, Journal of
Molecular Biology 290 (1): 331-345 (1999)
Tatford O.C.; Gomme P.T. and Bertolini J.:
Analytical techniques for the evaluation of liquid
protein
therapeutics, Biotechnol. Appl. Biochem Nr. 40:
67-81 (2004)
Fink, A.L.: Protein aggregation: folding
aggregates, inclusion bodies and amyloid. Fold
Des. 3 : R9 - R23, 1998
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
1.4 Immunogenicity observation - acute and/or sporadic
N/A
1.5 Immunogenicity observation - chronic and/or general
N/A
1.6 Immunogenicity assays
N/A
Page 10 of 46
Version 30 July 2010
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
2 Aggregate/Particle and long-term storage
2.1 Aggregate/Particle and molecular structure
N/A
2.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
N/A
2.3 Aggregate/Particle detection/characterization
N/A
2.4 Immunogenicity observation - acute and/or sporadic
N/A
2.5 Immunogenicity observation - chronic and/or general
Data
Source
In vivo
animal
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
influenza vaccines
Kim
Title
Stability Kinetics of Influenza
Vaccine Coated onto
Microneedles During Drying and
Storage
2.6 Immunogenicity assays
N/A
Page 11 of 46
Full citation
Y.-C. Kim, F.-S. Quan, R. W. Compans, S.-M. Kang, M. R.
Prausnitz: Stability Kinetics of Influenza Vaccine Coated onto
Microneedles During Drying and Storage, Pharmaceutical
Research (April 2010)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
Data
Source
In vitro
Substance
Class
Further substance
classification /
Substance name
Protein
Lactoferrin, ßLactoglobulin
In vitro
In vitro
Corresponding
author / Group
head
Title
Sarkar
Colloidal stability and interactions of
milk-protein-stabilized emulsions in
an artificial saliva
Seidler
Protein
alpha- synuclein
Munishkina
Identification and prediction of
promiscuous aggregating inhibitors
among known drugs
Conformational behavior and
aggregation of alpha-synuclein in
organic solvents: modeling the
effects of membranes
Full citation
A. Sarkar, K. K. T. Goh, H. Singh: Colloidal stability and
interactions of milk-protein-stabilized emulsions in an
artificial saliva, Food Hydrocolloids 23(5): 1270-1278
(2009)
J. Seidler, S. L. McGovern, T. N. Doman, B. K. Shoichet:
Identification and prediction of promiscuous aggregating
inhibitors among known drugs, Journal of Medicinal
Chemistry 46(21): 4477-4486 (2003)
L. A. Munishkina, C. Phelan, V. N. Uversky, A. L. Fink:
Conformational behavior and aggregation of alphasynuclein in organic solvents: modeling the effects of
membranes, Biochemistry 42(9): 2720-2730 (2003)
3.1 Aggregate/Particle and molecular structure
Data
Source
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
In vitro
Protein
Vicilin
Tang
In vitro
Peptide
Amyloid
Varela
In vitro
Protein
alpha- Amylase
Olsen
Title
Full citation
C.-H. Tang, L. Chen, C.-Y. Ma: Thermal aggregation,
amino acid composition and in vitro digestibility of vicilinThermal aggregation, amino acid
rich protein isolates from three Phaseolus legumes: A
composition and in vitro digestibility of
comparative study, Food Chemistry 113(4): 957-963
vicilin-rich protein isolates from three
Phaseolus legumes: A comparative study (2009)
A single mutation in an SH3 domain
L. Varela, B. Morel, A. I. Azuaga, F. Conejero-Lara: A
increases amyloid aggregation by
single mutation in an SH3 domain increases amyloid
accelerating nucleation, but not by
aggregation by accelerating nucleation, but not by
destabilizing thermodynamically the
destabilizing thermodynamically the native state, FEBS
native state
Letters 583(4): 801-806 (2009)
S. N. Olsen, K. B. Andersen, T. W. Randolph, J. F.
Carpenter, P. Westh: Role of electrostatic repulsion on
Role of electrostatic repulsion on colloidal colloidal stability of Bacillus halmapalus alpha-amylase,
stability of Bacillus halmapalus alphaBiochimica et Biophysica Acta (BBA) - Proteins &
amylase
Proteomics 1794(7): 1058-1065 (2009)
Page 12 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
3.2 Aggregate/Particle and long-term storage
Data
Source
Substance
Class
In vitro
in vitro
Protein
In vitro
Further substance
classification /
Substance name
Corresponding
author / Group
head
AAV2
Wright
recombinant
Human Flt3 Ligand Remmele Jr.
AAV2
Wright
Title
Full citation
J. F. Wright, T. Le, J. Prado, J. Bahr-Davidson, P. H. Smith, Z.
Identification of factors that contribute Zhen, J. M. Sommer, G. F. Pierce, G. Qu: Identification of
to recombinant AAV2 particle
factors that contribute to recombinant AAV2 particle
aggregation and methods to prevent aggregation and methods to prevent its occurrence during
its occurrence during vector
vector purification and formulation, Molecular Therapy 12(1):
171-178 (2005)
purification and formulation
Minimization of recombinant Human
R. L. Remmele Jr., S. D. Bhat, D. H. Phan, W. R. Gombotz:
Flt3 Ligand Aggregation at the Tm
Minimization of recombinant Human Flt3 Ligand Aggregation
plateau: A matter of thermal
at the Tm plateau: A matter of thermal reversibility,
reversibility
Biochemistry 38(16): 5241-5247 (1999)
J. F. Wright, T. Le, J. Prado, J. Bahr-Davidson, P. H. Smith, Z.
Identification of factors that contribute Zhen, J. M. Sommer, G. F. Pierce, G. Qu: Identification of
factors that contribute to recombinant AAV2 particle
to recombinant AAV2 particle
aggregation and methods to prevent aggregation and methods to prevent its occurrence during
vector purification and formulation, Molecular Therapy 12(1):
its occurrence during vector
purification and formulation
171-178 (2005)
3.3 Aggregate/Particle detection/characterization
Data
Source
In vitro
In vitro
In vitro
Substance
Class
Antibody
Protein
Protein
Further substance
classification /
Substance name
Antibody IgG
Lysozyme
soy protein
Corresponding
author / Group
head
Title
Hawe
Structural properties of monoclonal
antibody aggregates induced by freezethawing the thermal stress
Bangali
Biospecific Protein Immobilization for
Rapid Analysis of Weak Protein
Interactions Using Self-Interaction
Nanoparticle Spectroscopy
Tang
Effect of high pressure treatment on
aggregation and structural properties of
soy protein isolate
Page 13 of 46
Full citation
A. Hawe, J. C. Kasper, W. Friess, W. Jiskoot:
Structural properties of monoclonal antibody
aggregates induced by freeze-thawing the thermal
stress, European Journal of Pharmaceutical Sciences
38(2): 79-87 (2009)
A. N. Bengali, P. M. Tessier: Biospecific Protein
Immobilization for Rapid Analysis of Weak Protein
Interactions Using Self-Interaction Nanoparticle
Spectroscopy, Biotechnology and Bioengineering 104
(2): 240-250 (2009)
C.-H. Tang, C.-Y. Ma: Effect of high pressure
treatment on aggregation and structural properties of
soy protein isolate, LWT - Food Science and
Technology 42 (2): 606-611 (2009)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
In vitro
In vitro
Antibody
In vitro
α-lactalbumin
McGuffrey
Methylcellulose
Funami
HBsAg
Li
Copolymer
Xu
In vitro
Protein
In vitro
Protein
Amyloid
In vitro
Protein
β- Lactoglobulin
Akkermans
In vitro
Protein
Interferon- tau
Katayama
In vitro
Tjernberg
Lambeth
Version 30 July 2010
M. K. McGuffey, D. E. Otter, J. H. van Zanten, E. A.
Foegeding: Solubility and aggregation of commercial
Solubility and aggregation of commercial alpha-lactalbumin at neutral pH, International Dairy
alpha-lactalbumin at neutral pH
Journal 17(10): 1168-1178 (2007)
T. Funami, Y. Kataoka, M. Hiroe, I. Asai, R.
Takahashi, K. Nishinari: Thermal aggregation of
Thermal aggregation of methylcellulose
methylcellulose with different molecular weights, Food
with different molecular weights
Hydrocolloids 21(1): 46-58 (2007)
Y. Li, J. Bi, W. Zhou, Y. Huang, L. Sun, A.-P. Zeng,
G. Ma, Z. Su: Characterization of the large size
Characterization of the large size
aggregation of Hepatitis B virus surface
aggregation of Hepatitis B virus surface antigen
(HBsAg) formed in ultrafiltration process, Process
antigen (HBsAg) formed in ultrafiltration
process
Biochemistry 42(3): 315-319 (2007)
Y. Xu, L. Shi, R. Ma, W. Zhang, Y. An, X. X. Zhu:
Synthesis and micellization of thermo-and Synthesis and micellization of thermo-and pHpH-responsive block copolymer of poly(N- responsive block copolymer of poly(Nisopropylacrylamide)-block-poly(4-vinylpyridine),
isopropylacrylamide)-block-poly(4vinylpyridine)
Polymer 48(6): 1711-1717 (2007)
A. Tjernberg, N. Markova, W. J. Griffiths, D. Hallén:
DMSO-related effects in protein characterization,
DMSO-related effects in protein
Journal of Biomolecular Screening 11: 131-137
characterization
(2006)
B. Morel, S. Casares, F. Conejero-Lara: A Single
Mutation Induces Amyloid Aggregation in the αA Single Mutation Induces Amyloid
Aggregation in the α-Spectrin SH3
Spectrin SH3 Domain: Analysis of the Early Stages of
Fibril Formation, Journal of Molecular Biology 356(2):
Domain: Analysis of the Early Stages of
Fibril Formation
453-468 (2006)
C. Akkermans, P. Venema, S. S. Rogers, A. J. van
der Goot, R. M. Boom, E. van der Linden: Shear
Pulses Nucleate Fibril Aggregation, Food Biophysics
Shear Pulses Nucleate Fibril Aggregation 1(3): 144-150 (2006)
D. S. Katayama, R. Nayar, D. K. Chou, J. J. Valente,
J. Cooper, C. S. Henry, D. G. Vander Velde, L.
Villarete, C. P. Liu, M. C. Manning: Effect of Buffer
Species on the Thermally Induced Aggregation of
Effect of Buffer Species on the Thermally Interferon-tau, Journal of Pharmaceutical Sciences
Induced Aggregation of Interferon-tau
95(6): 1212-1226 (2006)
R. H. Lambeth, S. Ramakrishnan, R. Mueller, J. P.
Poziemsky, G. S. Miguel, L. J. Markoski, C. F.
Zukoski, J. S. Moore: Synthesis and aggregation
behavior of thermally responsive star polymers,
Synthesis and aggregation behavior of
thermally responsive star polymers
Langmuir 22(14): 6352-6360 (2006)
Page 14 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
buckwheat globulin
Choi
In vitro
Protein
Amyloid-beta(1-40)
Rangachari
In vitro
Protein
Heat shock proteins
Cashikar
In vitro
Protein
bovine α-lactalbumin
Otte
Xyloglucan
Freitas
In vitro
In vitro
Protein
alpha-synuclein
Uversky
In vitro
Protein
carbonic anhydrase
Nomura
NNRTI
Frenkel
Simulated
data
Version 30 July 2010
S.-M. Choi, C.-Y. Ma: Study of thermal aggregation of
globulin from common buckwheat (Fagopyrum
Study of thermal aggregation of globulin
esculentum Moench) by size-exclusion
from common buckwheat (Fagopyrum
chromatography and laser light scattering, Journal of
esculentum Moench) by size-exclusion
Agricultural and Food Chemistry 54(2): 554-561
chromatography and laser light scattering (2006)
V. Rangachari, D. K. Reed, B. D. moore, T. L.
Rosenberry: Secondary structure and interfacial
Secondary structure and interfacial
aggregation of amyloid-beta(1-40) on sodium dodecyl
aggregation of amyloid-beta(1-40) on
sulfate micelles, Biochemistry 45(28): 8639-8648
sodium dodecyl sulfate micelles
(2006)
A. G. Cashikar, M. Duennwald, S. L. Lindquist: A
chaperone pathway in protein disaggregation: hsp26
A chaperone pathway in protein
disaggregation: hsp26 alters the nature of alters the nature of protein aggregates to facilitate
reactivation by hsp104s, Journal of Biological
protein aggregates to facilitate
Chemistry 280(25): 23869-23875
reactivation by hsp104s
J. Otte, R. Ipsen, R. Bauer, M. J. Bjerrum, R.
Waninge: Formation of amyloid-like fibrils upon
Formation of amyloid-like fibrils upon
limited proteolysis of bovine α-lactalbumin,
limited proteolysis of bovine α-lactalbumin International Dairy Journal 15(3): 219-229 (2005)
R. A. Freitas, S. Martin, G. L. Santos, F. Valenga, M.
S. Buckeridge, F. Reicher, M.-R. Sierakowski:
Physico-chemical properties of seed xyloglucans from
different sources, Carbohydrate Polymers 60: 507Physico-chemical properties of seed
514 (2005)
xyloglucans from different sources
V. N. Uversky, G. Yamin, L. A. Munishkina, M. A.
Karymov, I S. Millett, S. Doniach, Y. L. Lyubchenko,
A. L. Fink: Effects of nitration on the structure and
aggregation of alpha-synuclein, Molecular Brain
Effects of nitration on the structure and
Research 134: 84-102 (2005)
aggregation of alpha-synuclein
Y. Nomura, Y. Sasaki, M. Takagi, T. Narita, Y.
Thermoresponsive controlled association Aoyama, K. Akiyoshi: Thermoresponsive controlled
of protein with a dynamic nanogel of
association of protein with a dynamic nanogel of
hydrophobized polysaccharide and cyclodextrin: heat
hydrophobized polysaccharide and
cyclodextrin: heat shock protein-like
shock protein-like activity of artificial molecular
chaperone, Biomacromolecules 6(1): 447-452 (2005)
activity of artificial molecular chaperone
Y. V. Frenkel, A. D. Clark, Jr., K. Das, Y.-H. Wang, P.
J. Lewi, P. A. J. Janssen, E. Arnold: Concentration
Concentration and pH dependent
and pH dependent aggregation of hydrophobic drug
aggregation of hydrophobic drug
molecules and relevance to oral bioavailability,
molecules and relevance to oral
Journal of Medicinal Chemistry 48(6): 1974-1983
bioavailability
(2005)
Page 15 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
maltodxtrin,
isoamylase
In vitro
In vitro
In vitro
In vitro
metallofullerene
Protein
Protein
Malate dehyrogenase
sophoragrin
Pohu
Split crystallization during debranching of
maltodextrins at high concentration by
isoamylase
Sitharaman
[email protected][C(COOH)2]10 and
[email protected](OH)X: nanoscale aggregation
studies of two metallofullerene MRI
contrast agents in aqueous solution
Schlieker
Solubilization of aggregated proteins by
ClpB/DnaK relies on the continuous
extraction of unfolded polypeptides
Ueda
Solubility-insolubility interconversion of
sophoragrin, a mannose/glucose-specific
lectin in sophora japonica (Japanese
pagoda tree) bark, regulated by the
sugar-specific interaction
In vitro
Protein
whey protein
de la Fuente
Influence of kappa-carrageenan on the
aggregation behaviour of proteins in
heated whey protein isolate solutions
In vitro
Protein
oat globulin
Zhao
Study of thermal aggregation of oat
globulin by laser light scattering
Mogk
Refolding of substrates bound to small
Hsps relies on a disaggregation reaction
mediated most efficiently by ClpB/DnaK
Picout
Pressure cell assisted solubilization of
xyloglucans: tamarind seed
polysaccharide and detarium gum
Andya
Mechanisms of aggregate formation and
carbohydrate excipient stabilization of
lyophilized humanized monoclonal
antibody formulations
In vitro
Protein
In vitro
In vitro
polysaccaride
Antibody
Page 16 of 46
Version 30 July 2010
A. Pohu,V. Planchot, J. L. Putaux, P. Colonna, A.
Buléon: Split crystallization during debranching of
maltodextrins at high concentration by isoamylase,
Biomacromolecules 5(5): 1792-1798 (2004)
B. Sitharaman, R. D. Bolskar, I. Rusakova, L. J.
Wilson: [email protected][C(COOH)2]10 and [email protected](OH)X:
nanoscale aggregation studies of two metallofullerene
MRI contrast agents in aqueous solution, Nano
Letters 4(12): 2373-2378 (2005)
C. Schlieker, I. Tews, B. Bukau, A. Mogk:
Solubilization of aggregated proteins by ClpB/DnaK
relies on the continuous extraction of unfolded
polypeptides, FEBS Letters 578(3): 351-356 (2005)
H. Ueda, H. Fukushima, Y. Hatanaka, H. Ogawa:
Solubility-insolubility interconversion of sophoragrin, a
mannose/glucose-specific lectin in sophora japonica
(Japanese pagoda tree) bark, regulated by the sugarspecific interaction, Biochemical Journal 382(Pt 3):
821-829 (2004)
M.A. de la Fuente, Y. Hemar, H. Singh: Influence of
kappa-carrageenan on the aggregation behaviour of
proteins in heated whey protein isolate solutions,
Food Chemistry 86(1): 1-9 (2004)
Y. Zhao, Y. Mine, C.-Y. Ma: Study of thermal
aggregation of oat globulin by laser light scattering,
Journal of Agricultural Food Chemistry 52(10): 30893096 (2004)
A. Mogk, C. Schlieker, K. L. Friedrich, H.-J.
Schönfeld, E. Vierling, B. Bukau: Refolding of
substrates bound to small Hsps relies on a
disaggregation reaction mediated most efficiently by
ClpB/Dank, Journal of Biological Chemistry 278(33):
31033-31042 (2003)
D. R. Picout, S. B. Ross-Murphy, N. Errington, S. E.
Harding: Pressure cell assisted solubilization of
xyloglucans: tamarind seed polysaccharide and
detarium gum, Biomacromolecules 4(3): 799807(2003)
J. D. Andya, C. C. Hsu, S. J. Shire: Mechanisms of
aggregate formation and carbohydrate excipient
stabilization of lyophilized humanized monoclonal
antibody formulations, AAPS PharmSci 5(2): 1-11
(2003)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Copolymer
Yamauchi
In vitro
Protein
Whey
Kazmierski
In vitro
Protein
ovalbumin
Weijers
copolymer
Pispas
In vitro
In vitro
Protein
Subtilisin
Pan
In vitro
Peptid
colony stimulating
factor
Bartkowski
In vitro
Protein
gelatine
Tromp
guar gum
Picout
In vitro
In vitro
Protein
Thaumatin
Iulek
In vitro
Protein
sHsp
Usui
Version 30 July 2010
K. Yamauchi, J. R. Lizotte, T. E. Long:
Thermoreversibile poly(alkyl acrylates) consisting of
self-complimentary multiple hydrogen bonding,
Macromolecules 36(4): 1083-1088 (2003)
M. Kazmierski, M. Corredig: Characterization of
soluble aggregates from whey protein isolate, Food
Characterization of soluble aggregates
from whey protein isolate
Hydrocolloids 17(5): 685-692 (2003)
M. Weijers, P. A. Barneveld, M. A. C. Stuart, R. W.
Visschers: Heat-induced denaturation and
Heat-induced denaturation and
aggregation of ovalbumin at neutral pH described by
aggregation of ovalbumin at neutral pH
irreversible first-order kinetics, Protein Science
described by irreversible first-order
12(12): 2693-703 (2003)
kinetics
Aggregation behavior of poly(butadieneS. Pispas, N. Hadjichristidis: Aggregation behavior of
b-ethylene oxide) block copolymers in
poly(butadiene-b-ethylene oxide) block copolymers in
dilute aqueous solutions: effect of
dilute aqueous solutions: effect of concentration,
concentration, temperature, ionic
temperature, ionic strength, and type of surfactant,
strength, and type of surfactant
Langmuir 19(1): 48-54 (2003)
X. Pan, C. E. Glatz: Solvent effects on the second
virial coefficient of subtilisin and solubility, Crystal
Solvent effects on the second virial
coefficient of subtilisin and solubility
Growth and Design 3(2): 203-207 (2003)
R. Bartkowski, R. Kitchel, N. Peckham, L. Margulis:
Aggregation of recombinant bovie granulocyte colony
Aggregation of recombinant bovie
granulocyte colony stimulating factor in
stimulating factor in solution, Journal of Protein
Chemistry 21(3): 137-143 (2002)
solution
R. H. Tromp, E. ten Grotenhuis, C. Olieman: Selfaggregation of gelatine above the gelling temperature
Self-aggregation of gelatine above the
gelling temperature analysed by SECanalysed by SEC-MALLS, Food Hydrocolloids 16(3):
235-239 (2002)
MALLS
D. R. Picout, S. B. Ross-Murphy, N. Errington, S. E.
Pressure cell assisted solution
Harding: Pressure cell assisted solution
characterization of polysaccharides. 1. Guar gum,
characterization of polysaccharides. 1.
Guar gum
Biomacromolecules 2(4): 1301-1309 (2001)
J. Iulek, A. M. Carcamo: The influence of precipitant
The influence of precipitant and thaumatin and thaumatin concentration on the protein
concentration on the protein aggregation
aggregation state at low ionic strengths, Publicatio
UEPG - Biological and Health Science 7(1): 91-98
state at low ionic strengths
Small heat shock proteins of a
K. Usui, T. Yoshida, T. Maruyama, M. Yohda: Small
hyperthermophilic archaeum,
heat shock proteins of a hyperthermophilic archaeum,
Thermococcus sp. Strain KS-1, Exists as Thermococcus sp. Strain KS-1, Exists as a spherical
a spherical 24 mer and its expression is
24 mer and its expression is highly induced under
highly induced under heat-stress
heat-stress conditions, Journal of Bioscience and
conditions
Bioengineering 92(2): 161-166 (2001)
Thermoreversibile poly(alkyl acrylates)
consisting of self-complimentary multiple
hydrogen bonding
Page 17 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
In vitro
In vitro
In vitro
In vitro
Cyclodextrin
Protein
beta-lactoglobulin
Protein
beta-lactoglobulin
Protein
beta-, alphalactoglobulin
Protein
Protein
In vitro
bovine serum albumin
Beta- lactoglobulin
Aeromonas gum
Sharma
Influence of cylodextrin ring substituents
on folding-related aggregation of bovine
carbonic anhydrase
Carrotta
Conformational characterization of
oligomeric intermediates and aggregates
in beta-lactoglobulin heat aggregation
Schokker
Heat-induced aggregation of betalactoglobulin AB at pH 2.5 as influenced
by ionic strength and protein
concentration
Schokker
Heat-induced aggregation of betalactoglobulin A and B with alphalactalbumin
Nishimura
Aggregation behaviour of bovine serum
albumin as a cause of sauce liquid
separation by heating
Bauer
Characterization and isolation of
intermediates in beta-lactoglobulin heat
aggregation at high pH
Xu
Aggregation and disaggregation of
Aeromonas gum in an aqueous solution
under different conditions
In vitro
Protein
beta-lactoglobulin
Schokker
Characterization of intermediates formed
during heat-induced aggregation of betalactoglobulin AB at neutral pH
In vitro
Protein
Rnase, human serum
albumin
Sah
Protein Behavior at the Water/Methylene
Chloride Interface
In vitro
Protein
beta-lactoglobulin
Hoffmann
Heat-induced aggregation of betalactoglobulin as a function of pH
Page 18 of 46
Version 30 July 2010
L. Sharma, A. Sharma: Influence of cylodextrin ring
substituents on folding-related aggregation of bovine
carbonic anhydrase, Euopean Journal of
Biochemistry 268(8): 2456-2463 (2001)
R. Carrotta, R. Bauer, R. Waninge, C. Rischel:
Conformational characterization of oligomeric
intermediates and aggregates in beta-lactoglobulin
heat aggregation, Protein Science 10(7): 1312-1318
(2001)
E. P. Schokker, H. Singh, D. N. Pinder, L. K.
Creamer: Heat-induced aggregation of betalactoglobulin AB at pH 2.5 as influenced by ionic
strength and protein concentration, International Dairy
Journal 10(4): 233-240 (2000)
E. P. Schokker, H. Singh, L. K. Creamer: Heatinduced aggregation of beta-lactoglobulin A and B
with alpha-lactalbumin, International Dairy Journal
10(12): 843-853 (2000)
K. Nishimura, M. Goto, T. Higasa, S. Kawase, Y.
Matsumura: Aggregation behaviour of bovine serum
albumin as a cause of sauce liquid separation by
heating, Journal of the Science of Food and
Agriculture 81(1): 76-81 (2001)
R. Bauer, R. Carrotta, C. Rischel, L. Øgendal:
Characterization and isolation of intermediates in
beta-lactoglobulin heat aggregation at high pH,
Biophysical Journal 79(2): 1030-1038 (2000)
X. Xu, L. Zhang: Aggregation and disaggregation of
Aeromonas gum in an aqueous solution under
different conditions, Journal of Polymer Science: Part
B: Polymer Physics 38(20): 2644-2651 (2000)
E. P. Schokker, H. Singh, D. N. Pinder, G. E. Norris,
L. K. Creamer: Characterization of intermediates
formed during heat-induced aggregation of betalactoglobulin AB at neutral pH, International Dairy
Journal 9(11): 791-800 (1999)
H. Sah: Protein Behavior at the Water/Methylene
Chloride Interface, Journal of Pharmaceutical
Sciences 88(12): 1320-1325 (1999)
M. A. M. Hoffmann, P. J. J. M. van Mil: Heat-induced
aggregation of beta-lactoglobulin as a function of pH,
Journal of Agricultural and Food Chemistry 47(5):
1898-1905 (1999)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
mannitol permease
Broos
A mechanism to alter reversibly the
oligomeric state of a membrane-bound
protein demonstrated with Escherichia
coli EIImtl in solution
In vitro
Protein
beta-lactoglobulin
Bauer
Detection of intermediate oligomers,
important for the formation of heat
aggregates of beta-lactoglobulin
In vitro
Protein
beta-lactoglobulin
Hoffmann
Molecular mass distributions of heatinduced beta-lactoglobulin aggregates
Protein
Lysozyme
Kuwamoto
Radiation damage to a protein solution,
detected by synchrotron X-ray smallangle scattering: dose-related
considerations and suppression by
cryoprotectants
In vitro
Protein
phytase, acid
phosphatase
GrueningerLeitch
Deglycosylation of proteins for
crystallization using recombinant fusion
protein glycosidases
in vitro
Protein
egg white
Mine
Effect of pH during the dry heating on the
gelling properties of egg white proteins
Zhang
A new strategy for enhancing the stability
of lyophilized protein: The effect of the
reconstitution Medium on keratinocyte
growth factor
In vitro
Protein
keratinocytegrowth
factor
In vitro
Antibody
monoclonal IgM antigroup B
Streptococcus
antibody
Gombotz
The stabilization of a human IgM
monoclonal antibody with
poly(vinlypyrrolidone)
In vitro
Antibody
IgG
Bee
Response of a Concentrated Monoclonal
Antibody Formulation to High Shear
In vitro
Page 19 of 46
Version 30 July 2010
J. Broos, R. T. Hoeve-Duurkens, G. T. Robillard: A
mechanism to alter reversibly the oligomeric state of a
membrane-bound protein demonstrated with
Escherichia coli EIImtl in solution, Journal of
Biological Chemistry 273(7): 3865-3870 (1998)
R. Bauer, S. Hansen, L. Øgendal: Detection of
intermediate oligomers, important for the formation of
heat aggregates of beta-lactoglobulin, International
Dairy Journal 8(2): 105-112 (1998)
M. A. M. Hoffmann, G. Sala, C. Olieman, K. G. de
Kruif: Molecular mass distributions of heat-induced
beta-lactoglobulin aggregates, Journal of Agricultural
and Food Chemistry 45 (8): 2949–2957 (1997)
S. Kuwamoto, S. Akiyama, T. Fujisawa: Radiation
damage to a protein solution, detected by synchrotron
X-ray small-angle scattering: dose-related
considerations and suppression by cryoprotectants,
Journal of Synchrotron Radiation 11(6): 462-468
(1997)
F. Grueninger-Leitch, A. D'Arcy, B. D'Arcy, C.
ChèneDeglycosylation of proteins for crystallization
using recombinant fusion protein glycosidases,
Protein Science 5(12): 2617–2622 (1996)
Y. Mine: Effect of pH during the dry heating on the
gelling properties of egg white proteins, Food
Research International 29(2): 155-161 (1996)
M. Z. Zhang, J. Wen. T. Arakawa, S. J. Prestrelski: A
new strategy for enhancing the stability of lyophilized
protein: The effect of the reconstitution Medium on
keratinocyte growth factor, Pharmaceutical Research
12(10): 1447-1452 (1995)
W. R. Gombotz, S. C. Pankey, D. Phan, R. Drager, K.
Donaldson, K. P. Antonsen, A. S. Hoffman, H. V.
Raff: The stabilization of a human IgM monoclonal
antibody with poly(vinlypyrrolidone), Pharmaceutical
Research 11(5): 624-632 (1994)
J. S. Bee, J. L. Stevenson, B. Mehta, J. Svitel, J.
Pollastrini, R. Platz, E. Freund, J. F. Carpenter, T. W.
Randolph: Response of a Concentrated Monoclonal
Antibody Formulation to High Shear, Biotechnology
and Bioengineering 103(5): 936-943 (2009)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
Whey protein
Flett
In vitro
Protein
Soy protein
Keerati-u-rai
in vitro
Sulfobetain
Che
In vitro
zero-valent iron
Tiraferri
beta- lactoglobulin,
alpha- lactoglobulin
Vardhanabhuti
In vitro
Protein
In vitro
Protein
In vitro
Peptid
In vitro
Protein
Salgado
In vitro
Protein
Salgado
In vitro
Protein
Coan
Amyloid Abeta
BSA
Bateman
Bagger
Version 30 July 2010
K. L. Flett, M. Corredig: Whey protein aggregate
formation during heating in the presence of KWhey protein aggregate formation during carrageenan, Food chemistry 115(4): 1479-1485
heating in the presence of K-carrageenan (2009)
M. Keerati-u-rai, M. Corredig: Effect of Dynamic High
Pressure Homogenization on the Aggregation State
Effect of Dynamic High Pressure
Homogenization on the Aggregation State of Soy Protein, Journal of Agricultural and Food
Chemistry 57(9): 3556-3562 (2009)
of Soy Protein
Y.-J. Che, Y. Tan, J. Cao, G.-Y. Xu: A study of
aggregation behavior of a sulfobetaine copolymer in
A study of aggregation behavior of a
dilute solution, Journal of Polymer Research: online
sulfobetaine copolymer in dilute solution
(2009)
A. Tiraferri, K. L. Chen, R. Sethi, M. Elimelech:
Reduced aggregation and sedimentation of zeroReduced aggregation and sedimentation valent iron nanoparticles in the presence of guar gum,
of zero-valent iron nanoparticles in the
Journal of Colloid and Interface Science 324(1-2): 71presence of guar gum
79 (2008)
B. B. Vardhanabhuti, E. A. Foegeding: Effects of
Effects of dextran sulfate, NaCl, and initial dextran sulfate, NaCl, and initial protein concentration
protein concentration on thermal stability
on thermal stability of beta-lactoglobulin and alphalactalbumin at neutral pH, Food Hydrocolloids 22(5):
of beta-lactoglobulin and alphalactalbumin at neutral pH
752-762 (2008)
K. E. D. Coan, B. K. Shoichet: Stoichiometry and
Physical Chemistry of Promiscuous Aggregate-Based
Stoichiometry and Physical Chemistry of
Inhibitors, Journal of the American Chemical Society
Promiscuous Aggregate-Based Inhibitors 130(29): 9606-9612 (2008)
D. A. Bateman, J. McLaurin, A. Chakrabartty:
Requirement of aggregation propensity of Requirement of aggregation propensity of Alzheimer
Alzheimer amyloid peptides for neuronal
amyloid peptides for neuronal cell surface binding,
BMC Neuroscience 8(29): 1-13 (2007)
cell surface binding
E. N. Salgado, J. Faraone-Mennella, F. A. Tezcan:
Controlling Protein-Protein Interactions through Metal
Controlling Protein-Protein Interactions
Coordination: Assembly of a 16-Helix Bundle Protein,
through Metal Coordination: Assembly of Journal of the American Chemical Society 129(44):
a 16-Helix Bundle Protein
13374-13375 (2007)
E. N. Salgado, J. Faraone-Mennella, F. A. Tezcan:
Supplemental information for: Controlling Supplemental information for: Controlling ProteinProtein-Protein Interactions through Metal Protein Interactions through Metal Coordination:
Assembly of a 16-Helix Bundle Protein, Journal of the
Coordination: Assembly of a 16-Helix
Bundle Protein
American Chemical Society 129(44): S1-S8 (2007)
H. L. Bagger, L. H. Øgendal, P. Westh: Solute effects
on the irreversible aggregation of serum albumin,
Solute effects on the irreversible
aggregation of serum albumin
Biophysical Chemistry 130(1-2): 17-25 (2007)
Page 20 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Protein
In vitro
In vitro
In vitro
In vitro
Ver Meer
Effect of Mesoporosity on Thermal and
Mechanical Properties of
Polystyrene/Silica Composites
Hepatitis B Antigen
Li
Characterization of the large size
aggregation of Hepatitis B virus surface
antigen (HBsAg) formed in ultrafiltration
process
Acylated chitosan
Hu
Self-aggregation and antibacterial activity
of N-acylated chitosan
Bateman
Requirement of aggregation propensity of
Alzheimer amyloid peptides for neuronal
cell surface binding
Ueda
Solubility-insolubility interconversion of
sophoragrin, a mannose/glucose-specific
lectin in sophora japonica (Japanese
pagoda tree) bark, regulated by the
sugar-specific interaction
Meyer
Protein purification by fusion with an
environmentally responsive elastin-like
polypeptide: effect of polypeptide length
on the purification of thioredoxin
prion protein
Polystyrene/Silica
Protein
In vitro
In vitro
Erlich
Complement Protein C1q Forms A
Complex With Cytotoxic Prion Protein
Oligomers
adenovirus -based
vaccine
In vitro
In vitro
Renteria
Development of a nasal adenovirusbased vaccine: Effect of concentration
and formulation on adenovirus stability
and infectious titer during actuation from
two delivery devices
Peptide
Protein
Protein
Amyloid
Sophoragrin
Thioreduxin
Page 21 of 46
Version 30 July 2010
S. S. Renteria, C. C. Clemens, M. A. Croyle:
Development of a nasal adenovirus-based vaccine:
Effect of concentration and formulation on adenovirus
stability and infectious titer during actuation from two
delivery devices, Vaccine 28(9): 2137-2148 (2010)
P. Erlich, C. Dumestre-Perard, W. L. Ling, C.
Lemaire-Vieille, G. Schoehn, G. J. Arlaud, N. M.
Thielens, J. Gagnon, J.-Y. Cesbron: Complement
Protein C1q Forms A Complex With Cytotoxic Prion
Protein Oligomers, The Journal of Biological
Chemistry 285: 19267-19276 (2010)
M. A. Ver Meer, B. Narasimhan, B. H. Shanks, S. K.
Mallapragada: Effect of Mesoporosity on Thermal and
Mechanical Properties of Polystyrene/Silica
Composites, Applied Materials & Interfaces 2(1): 4147
Y. Li, J. Bi, W. Zhou, Y. Huang, L. Sun, A.-P. Zeng,
G. Ma, Z. Su: Characterization of the large size
aggregation of Hepatitis B virus surface antigen
(HBsAg) formed in ultrafiltration process, Process
Biochemistry 42(3): 315-319 (2007)
Y. Hu, Y. Du, J. Yang, Y. Tang, J. Li, X. Wang: Selfaggregation and antibacterial activity of N-acylated
chitosan, Polymer 48(11): 3098-3106 (2007)
D. A. Bateman, J. McLaurin, A. Chakrabartty:
Requirement of aggregation propensity of Alzheimer
amyloid peptides for neuronal cell surface binding,
BMC Neuroscience 8(29): 1-13 (2007)
H. Ueda, H. Fukushima, Y. Hatanaka, H. Ogawa:
Solubility-insolubility interconversion of sophoragrin, a
mannose/glucose-specific lectin in sophora japonica
(Japanese pagoda tree) bark, regulated by the sugarspecific interaction, Biochemical Journal 382: 821-829
(2004)
D. E. Meyer, K. Trabbic-Carlson, A. Chilkoti: Protein
purification by fusion with an environmentally
responsive elastin-like polypeptide: effect of
polypeptide length on the purification of
thioredoxinvol, Biotechnology Progress 17(4): 720728 (2001)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
3.4 Immunogenicity observation - acute and/or sporadic
N/A
3.5 Immunogenicity observation - chronic and/or general
N/A
3.6 Immunogenicity assays
N/A
Page 22 of 46
Version 30 July 2010
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
4 Aggregate/Particle detection/characterization
Data Source
Substance
Class
In vitro
Protein
Further substance
classification /
Substance name
Capelle
In vitro
In vitro
Corresponding
author / Group
head
El Seoud
Calsequestrin
Shadle
in vitro
Lignin
Gidh
In vitro
Lignin
Gidh
In vitro
Lignin
Gidh
In vitro
No
experimental
data
Protein
Protein
Ye
Liu
Title
Full citation
M. A. H. Capelle, R. Gurny, T. Arvinte: High throughput
High throughput screening of protein screening of protein formulation stability: practical
considerations, European Journal of Pharmaceutics and
formulation stability: practical
considerations
Biopharmaceutics 65(2): 131-148 (2007)
O. A. El Seoud, P. A. R. Pires, T. Abdel-Moghny, E. L.
Bastos: Synthesis and micellar properties of surfaceSynthesis and micellar properties of active ionic liquids: 1-Alkyl-3-methylimidazolium
surface-active ionic liquids: 1-Alkyl- chlorides, Journal of colloid and Interface Science 313(1):
3-methylimidazolium chlorides
296-304 (2007)
S. E. Shadle, R. Rostock, L. Bonfrisco, M. E. Schimpf:
Study of Calsequestrin Aggregation by Flow Field-Flow
Study of Calsequestrin Aggregation Fractionation with Light Scattering Detection, Journal of
by Flow Field-Flow Fractionation
Liquid Chromatography & Related Technologies 30
with Light Scattering Detection
(9&10): 1513-1523 (2007)
A. V. Gidh, S. R. Decker, C. H. See, M. E. Himmel, C. W.
Williford: Characterization of lignin using multi-angle laser
Characterization of lignin using
multi-angle laser light scattering and light scattering and atomic force microscopy, Analytica
Chimica Acta 555(2): 250-258 (2006)
atomic force microscopy
A. V. Gidh, S. R. Decker, T. B. Vinzant, M. E. Himmel, C.
W. Williford: Fungal-induced redistribution of kraft lignin
Fungal-induced redistribution of kraft molecular weight by multi-angle laser light scattering,
lignin molecular weight by multiChemical Engineering Communications 193: 1546-1561
angle laser light scattering
(2006)
A. V. Gidh, S. R. Decker, T. B. Vinzant, M. E. Himmel, C.
Williford: Determination of lignin by size exclusion
Determination of lignin by size
exclusion chromatography using
chromatography using multi angle laser light scattering,
Journal of Chromatography A 1114(1): 102-110 (2006)
multi angle laser light scattering
Simultaneous determination of
H. Ye: Simultaneous determination of protein
protein aggregation, degradation,
and absolute molecular weight by
aggregation, degradation, and absolute molecular weight
size exclusion chromatographyby size exclusion chromatography-multiangle laser light
multiangle laser light scattering
scattering, Analytical Biochemistry 356: 76-85 (2006)
A critical review of analytical
J. Liu, J. D. Andya, S. J. Shire: A critical review of
ultracentrifugation and field flow
analytical ultracentrifugation and field flow fractionation
fractionation methods for measuring methods for measuring protein aggregation, The AAPS
protein aggregation
Journal 8(3): E580-E589 (2006)
Page 23 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Antibody
Moll
In vitro
Whittaker
In vitro
terbenzimidazoles
Khan
In vitro
Peptid
Novispirin G-10
Wimmer
In vitro
Protein
antifreeze
glycoprotein
Bouvet
In vitro
Protein
de Marco
In vitro
Protein
Schimmele
In vitro
Yao
In vitro
Sodium
dodecylsulfate
In vitro
DNA
Thévenot
Version 30 July 2010
J. R. Moll, V. Miranda, Y.-M. Li, L. Bergerud, T. M.
Spitznagel, M. P. Byrne: Characterization of Purified
Antibody Dimers (2006)
M. R. Whittaker, M. J. Monteiro: Synthesis and
aggregation behavior of four-arm star amphiphilic block
copolymers in water, Langmuir 22(23):9746-9752 (2006)
Q. A. Khan, C. M. Barbieri, A. R. Srinivasan, Y.-H. Wang,
E. J. LaVoie, D. S. Pilch: Drug self-association modulates
Drug self-association modulates the the cellular bioavailability of DNA minor groove-directed
cellular bioavailability of DNA minor terbenzimidazoles, Journal of Medicinal Chemistry
groove-directed terbenzimidazoles
49(17):5245-5251 (2006)
R. Wimmer, K. K. Andersen, B. Vad, M. Davidsen, S.
Mølgaard, L. W. Nesgaard, H. H. Kristensen, D. E.
Versatile interactions of the
Otzen: Versatile interactions of the antimicrobial peptide
antimicrobial peptide novispirin with novispirin with detergents and lipids, Biochemistry 45(2):
detergents and lipids
481-497 (2006)
V. R. Bouvet, G. R. Lorello, R. N. Ben: Aggregation of
Aggregation of antifreeze
antifreeze glycoprotein fraction 8 and its effect on
glycoprotein fraction 8 and its effect antifreeze activity, Biomacromolecules 7(2): 565on antifreeze activity
71(2006)
Native folding of aggregation-prone A. de Marco, L. Vigh, S. Diamant, P. Goloubinoff: Native
recombinant proteins in escherichia folding of aggregation-prone recombinant proteins in
coli by osmolytes, plasmid- or
escherichia coli by osmolytes, plasmid- or benzyl alcoholbenzyl alcohol-overexpressed
overexpressed molecular chaperones, Cell Stress &
molecular chaperones
Chaperones 10(4): 329–339 (2005)
B. Schimmele, N. Grafe, A. Pluckthun: Ribosome display
of mammalian receptor domains, Protein Engineering,
Ribosome display of mammalian
Design & Selection 18(6): 285-294 (2005)
receptor domains
B. Yao, B. Collins, M. Chen: Light scattering to detect
Light scattering to detect compound compound aggregation in screening assays, Drug Plus
International (2005)
aggregation in screening assays
C. Thévenot, B. Grassl, G. Bastiat, W. Binana:
Aggregation number and critical
Aggregation number and critical micellar concentration of
surfactant determined by time-dependent static light
micellar concentration of surfactant
determined by time-dependent static scattering (TDSLS) and conductivity, Colloids and
Surfaces A: Physicochemical Engineering Aspects 252:
light scattering (TDSLS) and
105-111 (2005)
conductivity
E. Tan, J. Wong, D. Nguyen, Y. Zhang, B. Erwin, L. K.
Van Ness, S. M. Baker, D. J. Galas, A. Niemz: Isothermal
Isothermal DNA amplification
DNA amplification coupled with DNA nanosphere-based
coupled with DNA nanospherecolorimetric detection, Analytical Chemistry 77(24): 7984based colorimetric detection
7992 (2005)
Characterization of Purified Antibody
Dimers
Synthesis and aggregation behavior
of four-arm star amphiphilic block
copolymers in water
Page 24 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Silver- colloid
Bengter
zFP538
Zubova
In vitro
Protein
In vitro
Protein
Shen
In vitro
Protein
Jancarik
In vitro
red blood cells
In vitro
Yun
In vitro
In vitro
Armstrong
Peptid
liposomes
Zhang
parathyroid hormone
Kamberi
New light on Ag-colloid preparation
for surface-enhanced FT-Raman
spectroscopy: the role of
aggregation
Version 30 July 2010
H. Bengter, C. Tengroth, S. P. Jacobsson: New light on
Ag-colloid preparation for surface-enhanced FT-Raman
spectroscopy: the role of aggregation, Journal of Raman
Spectroscopy 36: 1015-1022 (2005)
N. N. Zubova, V. A. Korolenko, A. A. Astafyev, A. N.
Petrukhin, L. M. Vinokurov, O. M. Sarkisov, A. P.
Brightness of yellow fluorescent
Savitsky: Brightness of yellow fluorescent protein from
protein from coral (zFP538)
coral (zFP538) depends on aggregation, Biochemistry
depends on aggregation
44(10): 3982-3993 (2005)
W. Shen, R. G. H. Lammertink, J. K. Sakata, J. A.
Kornfield, D. A. Tirrell: Assembly of an artificial protein
Assembly of an artificial protein
hydrogel through leucine zipper aggregation and disulfide
hydrogel through leucine zipper
bond formation, Macromolecules 38(9): 3909-3916
aggregation and disulfide bond
(2005)
formation
J. Jancarik, R. Pufan, C. Hong, S.-H. Kim, R. Kim:
Optimum solubility (OS) screening: an efficient method to
Optimum solubility (OS) screening:
optimize buffer conditions for homogeneity and
an efficient method to optimize
crystallization of proteins, Acta Crystallographica 60(Pt
buffer conditions for homogeneity
9): 1670-1673 (2004)
and crystallization of proteins
J. K. Armstrong, R. B. Wenby, H. J. Meiselman, T. C.
Fisher: The hydrodynamic radii of macromolecules and
The hydrodynamic radii of
macromolecules and their effect on their effect on red blood cell aggregation, Biophysical
Journal 87 (6): 4259-4270 (2004)
red blood cell aggregation
J. Yun, R. Faust, L. Sz. Szilágyi, S. Kéki, M. Zsuga:
Effect of architecture on the micellar Effect of architecture on the micellar properties of
amphiphilic block copolymers: comparison of AB linear
properties of amphiphilic block
copolymers: comparison of AB
diblock, A2B2, A3B3, and (AB)3 star block copolymers,
Journal of Macromolecular Science: Part A-Pure and
linear diblock, A2B2, A3B3, and
(AB)3 star block copolymers
Applied Chemistry 41(6): 613-627 (2004)
L. Zhang, T. Peng, S.-X. Cheng, R.-X Zhuo:
Destabilization of liposomes by
Destabilization of liposomes by uncharged hydrophilic
and amphiphilic polymers, Journal of Physical Chemistry
uncharged hydrophilic and
amphiphilic polymers
B 108(23): 7763-7770 (2004)
Analysis of non-covalent
M. Kamberi, P. Chung, R. DeVas, L. Li, Z. Li, X. Ma
aggregation of synthetic hPTH (1(Sharon), S. Fields, C. M. Riley: Analysis of non-covalent
34) by size-exclusion
aggregation of synthetic hPTH (1-34) by size-exclusion
chromatography and the importance chromatography and the importance of suppression of
of suppression of non-specific
non-specific interactions for a precise quantitation,
interactions for a precise
Journal of Chromatography B, Analytical technologies in
quantitation
the biomedical and life sciences 810(1): 151-155 (2004)
Page 25 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
superoxide
dismutase-1
Ray
In vitro
Copolymers
Annenkov
In vitro
ether-linked
fluorocarbon
Huang
lysozyme
Gu
Amylopectin
Olsson
Myosin
López-Díaz
Copolymer
Yun
In vitro
In vitro
Protein
Protein
In vitro
In vitro
Protein
In vitro
In vitro
In vitro
Protein
Rhazi
beta-cyclodextrin, Nacylurea
Soltés
An intersubunit disulfide bond
prevents in vitro aggregation of a
superoxide dismutase-1 mutant
linked to familial amytrophic lateral
sclerosis
Version 30 July 2010
S. S. Ray, R. J. Nowak, K. Strokovich, R. H. Brown, Jr.,
T. Walz, P. T. Lansbury, Jr.: An intersubunit disulfide
bond prevents in vitro aggregation of a superoxide
dismutase-1 mutant linked to familial amytrophic lateral
sclerosis, Biochemistry 43(17): 4899-4905 (2004)
V. V. Annenkov, E. N. Danilovtseva, H. Tenhu, V.
Aseyev, S.-P. Hirvonen, A. I. Mikhaleva: Copolymers of
Copolymers of 1-vinylimidazole and 1-vinylimidazole and (meth)acrylic acid: Synthesis and
(meth)acrylic acid: Synthesis and
polyelectrolyte properties, European Polymer Journal
polyelectrolyte properties
40(6): 1027-1032 (2004)
W. Huang, C. Jin, D. K. Derzon, T. A. Huber, J. A. Last,
P. P. Provencio, A. S. Gopalan, M. Dugger, D. Y. Sasaki:
Synthesis of ether-linked
fluorocarbon surfactants and their
Synthesis of ether-linked fluorocarbon surfactants and
their aggregational properties in organic solvents, Journal
aggregational properties in organic
solvents
of Colloid and Interface Science 272(2): 457-464 (2004)
Z. Gu, X. Zhu, S. Ni, Z. Su, H.-M. Zhou: Conformational
changes of lysozyme refolding intermediates and
Conformational changes of
lysozyme refolding intermediates
implications for aggregation and renaturation, The
and implications for aggregation and International Journal of Biochemistry & Cell Biology
renaturation
36(5): 795-805 (2004)
C. Olsson, T. Frigård, R. Andersson, A.-M. Hermansson:
Effects of amylopectin structure and Effects of amylopectin structure and molecular weight on
molecular weight on microstructural microstructural and rheological properties of mixed betaand rheological properties of mixed lactoglobulin gels, Biomacromolecules 4(5): 1400-1409
(2003)
beta-lactoglobulin gels
J. A. López-Díaz, A. Rodríguez-Romero, A. HernándezSantoyo, R. R. Sotelo-Mundo, A. M. Calderón de la
Effects of Soy Glycinin Addition on
Barca: Effects of Soy Glycinin Addition on the
the Conformation and Gel Strength
Conformation and Gel Strength of Two Pork Myosin
of Two Pork Myosin Types
Types, Journal of Food Science 68(9): 2724-2729 (2003)
Effect of architecture on the micellar J. Yun, R. Faust, L. Sz. Szilagyi, S. Keki, M. Zsuga:
properties of amphiphilic block
Effect of architecture on the micellar properties of
copolymers: comparison of AB
amphiphilic block copolymers: comparison of AB linear
linear diblock, A1A2B, and A2B
diblock, A1A2B, and A2B heteroarm star block
heteroarm star block copolymers
copolymers, Macromolecules 36(5): 1717-1723 (2003)
Sulfhydryl-disulfide changes in
storage proteins of developing
L. Rhazi, R. Cazalis, T. Aussenac: Sulfhydryl-disulfide
wheat grain: influence on the SDSchanges in storage proteins of developing wheat grain:
unextractable glutenin polymer
influence on the SDS-unextractable glutenin polymer
formation
formation, Journal of Cereal Science 38(3): 3-13 (2003)
Molecular characterization of two
L. Soltés, R. Mendichi: Molecular characterization of two
host–guest associating hyaluronan
host–guest associating hyaluronan derivatives,
derivatives
Biomedical Chromatography 17(6): 376-384 2003)
Page 26 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
Protein
In vitro
In vitro, In
vivo animal
Polysaccarides
Simon
Tau Protein
Yao
copolymers
Waddon
Protein
Thoma
In vitro
In vitro
amylopectin
Blennow
In vitro
cyclic amides
Pethica
In vitro
Pullulan
Duval
Discosomar
fluorescent protein
Mizuno
In vitro
Protein
Amphiphilic polysaccharides.
Evidence for a competition between
intra and intermolecular associations
in dilute system
Version 30 July 2010
S. Simon, J.Y. Dugast, D. Le Cerf, L. Picton, G. Muller:
Amphiphilic polysaccharides. Evidence for a competition
between intra and intermolecular associations in dilute
system, Polymer 44(26): 7917-7924 (2003)
T.-M. Yao, K. Tomoo, T. Ishida, H. Hasegawa, M. Sasaki,
T. Taniguchi: Aggregation Analysis of the Microtubule
Aggregation Analysis of the
Binding Domain in Tau Protein by Spectroscopic
Microtubule Binding Domain in Tau Methods, The Journal of Biochemistry 134(1): 91-99
Protein by Spectroscopic Methods
(2003)
A. J. Waddon, L. Zheng, R. J. Farris, E. B. Coughlin:
Nanostructured polyethylene-POSS Nanostructured polyethylene-POSS copolymers: control
copolymers: control of crystallization of crystallization and aggregation, Nano Letters 2(10):
and aggregation
1149-1155 (2002)
G. Thoma, A.G. Katopodis, N. Voelcker, R.O. Duthaler,
M.B. Streiff: Novel Glycodendrimers Self-Assemble to
Novel Glycodendrimers SelfAssemble to Nanoparticles which
Nanoparticles which Function as Polyvalent Ligands In
Vitro and In Vivo, Angewandte Chemie International
Function as Polyvalent Ligands In
Vitro and In Vivo
Edition 41(17): 3195-3198 (2002)
Sugar-based surfactants: adsorption R. C. Bazito, O. A. El Seoud: Sugar-based surfactants:
and micelle formation of sodium
adsorption and micelle formation of sodium methyl 2methyl 2-acylamido-2-deoxy-6-Oacylamido-2-deoxy-6-O-sulfo-D-glucopyranosides,
sulfo-D-glucopyranosides
Langmuir 18(11): 4362-4366 (2002)
Amylopectin aggregation as a
A. Blennow, A. M. Bay-Smidt, R. Bauer: Amylopectin
function of starch phophate content aggregation as a function of starch phophate content
studied by size exclusion
studied by size exclusion chromatography and on-line
chromatography and on-line
refractive index and light scattering, International Journal
refractive index and light scattering
of Biological Macromolecules 28(5): 409-420 (2001)
Surface and colloidal properties of
B. A. Pethica, L. Senak, Z. Zhu, A. Lou: Surface and
cyclic amides. 5. N-cyclohexyl-2colloidal properties of cyclic amides. 5. N-cyclohexyl-2pyrrolidone-water mixtures
pyrrolidone-water mixtures aggregation in solution and
aggregation in solution and
adsorption at the air-solution interface, Colloids and
adsorption at the air-solution
Surfaces A: Physiochemical and Engineering Aspects
interface
186(1-2): 113-122 (2001)
C. Duval, D. Le Cerf, L. Picton, G. Muller: Aggregation of
amphiphilic pullulan derivatives evidenced by on-line flow
Aggregation of amphiphilic pullulan
derivatives evidenced by on-line
field flow fractionation/multi-angle laser light scattering,
Journal of chromatography. B, Biomedical sciences and
flow field flow fractionation/multiangle laser light scattering
applications 753(1): 115-122 (2001)
Red fluorescent protein from
H. Mizuno, A. Sawano, P. Eli, H. Hama, A. Miyawaki:
Discosoma as a fusion tag and a
Red fluorescent protein from Discosoma as a fusion tag
partner for fluorescence resonance
and a partner for fluorescence resonance energy
energy transfer
transfer, Biochemistry 40(8): 2502-2510 (2001)
Page 27 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
humic acid
Manning
In vitro
Peptid
acylated peptide
Clodfelter
In vitro
Protein
interferon-γ
Kendrick
In vitro
antineoplastic glucan
(PS1A1)
Farrugia
In vitro
dioctyl-polyfluorene
Grell
apoprotein A-l
Bolaños-García
titania nanoparticles
Moran
In vitro
In vitro
Protein
In vitro
Wyatt
In vitro
Wyatt
Version 30 July 2010
T. J. Manning, T. Bennett, D. Milton: Aggregation studies
of humic acid using multiangle laser light scattering, The
Science of the Total Environment 257(2-3): 171-176
(2000)
D. K. Clodfelter, M. A. Nussbaum, J. Reilly: Comparison
Comparison of free solution capillary of free solution capillary electrophoresis and size
electrophoresis and size exclusion
exclusion chromatography for quantitating non-covalent
aggregation of an acylated peptide, Journal of
chromatography for quantitating
non-covalent aggregation of an
Pharmaceutical and Biomedical Analysis 19(5): 763-775
(1999)
acylated peptide
B. S. Kendrick, J. F. Carpenter, J. L. Cleland, T. W.
Randolph: A transient expansion of the native state
precedes aggregation of recombinant human interferonγ, Proceedings of the National Academy of Sciences of
A transient expansion of the native
state precedes aggregation of
the United States of America 95(24): 14142–14146
(1998)
recombinant human interferon-γ
Comparative measurement of the
I. V. Farrugia, E. J. Dadey, K. Ashline, M. J. Groves:
molecular weight of an
Comparative measurement of the molecular weight of an
antineoplastic glucan from BCG
antineoplastic glucan from BCG vaccine, The Journal of
vaccine
Pharmacy and Pharmacology 50(11): 1205-1211 (1998)
Chain geometry, solution
M. Grell, D. D. C. Bradley, X. Long, T. Chamberlain, M.
aggregation and enhanced
Inbasekaran, E. P. Woo, M. Soliman: Chain geometry,
dichroism in the liquid-crystalline
solution aggregation and enhanced dichroism in the
conjugated polymer poly(9,9liquid-crystalline conjugated polymer poly(9,9dioctylfluorene)
dioctylfluorene), Acta Polymerica 49(8): 439-444 (1998)
V. M. Bolaños-García, J. Mas-Oliva, M. Soriano-García,
A. Moreno: Precrystallization of human apoprotein A-I
Precrystallization of human
based on its aggregation behavior in solution studied by
apoprotein A-I based on its
dynamic light scattering, Journal of Molecular Structure
aggregation behavior in solution
440(1-3):1-8 (1998)
studied by dynamic light scattering
P. D. Moran, J. R. Bartlett, J. L. Woolfrey, G. A.
Bowmaker, R. P. Cooney: Formation and gelation of
Formation and gelation of titania
nanoparticles from AOT reverse
titania nanoparticles from AOT reverse micelles, Journal
of Sol-Gel Science and Technology 8(1-3): 65-69 (1997)
micelles
Multiangle light scattering combined P. J. Wyatt: Multiangle light scattering combined with
with HPLC -- LC GC back to the
HPLC -- LC GC back to the basics, LCGC 15: 160-168
basics
(1997)
Multiangle light scattering: The basic P. J. Wyatt: Multiangle light scattering: The basic tool for
tool for macromolecular
macromolecular characterization, Instrumentation
characterization
Science & Technology 25(1): 1-18 (1997)
Aggregation studies of humic acid
using multiangle laser light
scattering
Page 28 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
copolymers
Khougaz
In vitro
Pectins
Rinaudo
In vitro
poly (acrylamide)
Ying
human growth
hormone
DeFelippis
In vitro
κ- carrageenan
Viebke
In vitro
polystyrene
Zhong
In vitro
Protein
In vitro
Van Zanten
In vitro
cyclodextrin
In vitro
Salamone
In vitro
In vitro
Petter
Protein
gemini
pseudoglyceryl lipid
membrane
Bhattacharya
Succinylated Gelatin
Liu
Aggregation and critical Micelle
concentrations of polystyrene-bpoly(sodium acrylate) and
polystyrene-b-poly(acrylic acid)
Micelles in Organic Media
Version 30 July 2010
K. Khougaz, X. F. Zhong, A. Eisenberg: Aggregation and
critical Micelle concentrations of polystyrene-bpoly(sodium acrylate) and polystyrene-b-poly(acrylic
acid) Micelles in Organic Media, Macromolecules,
Macromolecules 29(11): 3937-3949 (1996)
M. Rinaudo: Physicochemical properties of pectins in
solution and gel states, Pectins and Pectinases 14: 21-34
Physicochemical properties of
(1996)
pectins in solution and gel states
Laser light scattering of
Q. Ying, G. Wu, B. Chu, R. Farinato, L. Jackson: Laser
poly(acrylamide) in 1 M NaCl
light scattering of poly(acrylamide) in 1 M NaCl aqueous
aqueous Solution
Solution, Macromolecules 29(13): 4646-4654 (1996)
M. R. DeFelippis, M. A. Kilcomons, M. P. Lents, K. M.
Youngman, H. A. Havel: Acid Stabilization of human
Acid Stabilization of human growth
hormone equilibrium folding
growth hormone equilibrium folding intermediates,
Biochimica et Biophysica acta BBA 1247(1):35-45 (1995)
intermediates
C. Viebke, L. Piculell, S. Nilsson: On the mechanism of
gelation of helix forming biopolymers, Macromolecules 27
On the mechanism of gelation of
helix forming biopolymers
(15): 4160–4166 (1994)
X. F. Zhong, A. Eisenberg: Aggregation and critical
Aggregation and critical micellization micellization behavior of carboxylate-terminated
behavior of carboxylate-terminated
monochelic polystyrene, Macromolecules 27 (7): 1751–
1758 (1994)
monochelic polystyrene
J. M. Van Zanten, M. Elimelech: Determination of
absolute coagulation rate constants by multiangle light
Determination of absolute
coagulation rate constants by
scattering, Journal of Colloid and Interface Science
154(1):1-7(1992)
multiangle light scattering
R. C. Petter, J. S. Salek, C. T. Sikorski, G. Kumaravel,
F.-T. Lin: Cooperative binding by aggregated mono-6Cooperative binding by aggregated (alkylamino)-β-cyclodextrins, Journal of the American
mono-6-(alkylamino)-β-cyclodextrins Chemical Society 112(10): 3860–3868 (1990)
J. C. Salamone, J. C., A. M. Thompson, C. H. Su, A. C.
Watterson: Associated Polymers in solution, American
Chemical Society Proc., Polym. Mat. Sci. Eng. 61: 518521(1988)
Associated Polymers in solution
Thermotropic and hydration studies S. Bhattacharya, A. Bajaj: Thermotropic and hydration
of membranes formed from gemini
studies of membranes formed from gemini
pseudoglyceryl lipids possessing
pseudoglyceryl lipids possessing polymethylene spacers,
polymethylene spacers
Langmuir 23(17): 8988-8994 (2007)
Determination of Modification
T. Liu, G.-F. Zhang, W.-B. Zhou, Z.-G. Su: Determination
Degree of Succinylated Gelatin by
of Modification Degree of Succinylated Gelatin by Size
Size Exclusion Chromatography
Exclusion Chromatography Coupled with Multi Angle
Coupled with Multi Angle Laser Light Laser Light Scattering, Chinese Journal of Analytical
Scattering
Chemistry 35(1): 43-48 (2007)
Page 29 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
In vitro
Antibody
IgG
Hawe
In vitro
Protein
Polyomavirus VP1
Lipin
Lipopolysaccarid
Sasaki
Amyloid Beta
Kotarek
Methylcellulose
Zhou
Rapid and quantitative
determination of critical micelle
concentration by automatic
continuous mixing and static light
scattering
Lipeo-sCT: A novel reversible
lipidized salmon calcitonin
derivative, its biophysical properties
and hypocalcemic activity
Characterization of High-MolecularWeight Nonnative Aggregates and
Aggregation Kinetics by Size
Exclusion Chromatography With
Inline Multi-Angle Laser Light
Scattering
Online fluorescent dye detection
method for the characterization of
immunoglobulin G aggregation by
size exclusion chromatography and
asymmetrical flow field flow
fractionation
Quaternary size distribution of
soluble aggregates of glutathione-Stransferase-purified viral protein as
determined by asymmetrical flow
field flow fractionation and dynamic
light scattering
Aggregation Behavior of an UltraPure Lipopolysaccharide that
Stimulates TLR-4 Receptors
Quartz crystal microbalance
analysis of growth kinetics for
aggregation intermediates of the
amyloid-beta protein
Microstructure and aggregation
behavior of methylcelluloses
prepared in NaOH/urea aqueous
solutions
Ishikawa
The Rough Endoplasmic Reticulumresident FK506-binding Protein
FKBP65 Is a Molecular Chaperone
That Interacts with Collagens
In vitro
Paillet
In vivo animal Peptid
In vitro
In vitro
Protein
In vitro
In vitro
Protein
Lipeo- salmon
calcitonin
Cheng
Li
FKBP65
Page 30 of 46
Version 30 July 2010
S. Paillet, B. Grassl, J. Desbrieres: Rapid and
quantitative determination of critical micelle concentration
by automatic continuous mixing and static light
scattering, Analytica Chimica Acta 636(2): 236-241
(2009)
W. Cheng, L.-Y. Lim: Lipeo-sCT: A novel reversible
lipidized salmon calcitonin derivative, its biophysical
properties and hypocalcemic activity, European Journal
of Pharmaceutical Sciences 37(2): 151-159 (2009)
Y. Li, W. F. Weiss IV, C. J. Roberts: Characterization of
High-Molecular-Weight Nonnative Aggregates and
Aggregation Kinetics by Size Exclusion Chromatography
With Inline Multi-Angle Laser Light Scattering, Journal of
Pharmaceutical Science 98(11): 3997-4016 (2009)
A. Hawe, W. Friess, M. Sutter, W. Jiskoot: Online
fluorescent dye detection method for the characterization
of immunoglobulin G aggregation by size exclusion
chromatography and asymmetrical flow field flow
fractionation, Analytical Biochemistry 378(2): 115-122
(2008)
D. I. Lipin, L. H. L. Lua, A. P. J. Middelberg: Quaternary
size distribution of soluble aggregates of glutathione-Stransferase-purified viral protein as determined by
asymmetrical flow field flow fractionation and dynamic
light scattering, Journal of Chromatography A 1190(1-2):
204-214 (2008)
H. Sasaki, S. H. White: Aggregation Behavior of an UltraPure Lipopolysaccharide that Stimulates TLR-4
Receptors, Biophysical Journal 95(2): 986-993 (2008)
J. A. Kotarek, K. C. Johnson, M. A. Moss: Quartz crystal
microbalance analysis of growth kinetics for aggregation
intermediates of the amyloid-beta protein, Analytical
Biochemistry 378(1): 15-24 (2008)
J. Zhou, Y. Xu, X. Wang, Y. Qin, L. Zhang: Microstructure
and aggregation behavior of methylcelluloses prepared in
NaOH/urea aqueous solutions, Carbohydrate Polymers
74(4): 901-906 (2008)
Y. Ishikawa, J. Vranka, J. Wirz, K. Nagata, H. P.
Bächinger: The Rough Endoplasmic Reticulum-resident
FK506-binding Protein FKBP65 Is a Molecular
Chaperone That Interacts with Collagens, The Journal of
Biological Chemistry 283(46): 31584-31590 (2008)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
alginic acid
Christensen
In vitro
cycoldextrin
Bartlett
In vitro
Borgstahl
In vitro
In vitro
Protein
In vitro
Protein
In vitro
Protein
In vivo animal Protein
lignin
Gidh
Human
Apolipoprotein
Moreno
0 Fields, G
Interferon gamma
Krishnan, S.
Interferon Alpha2b
Hermeling
Suzanne
Version 30 July 2010
Comment on "Conformational
changes and aggregation of alginic
acid as determined by fluorescence
correlation spectroscopy"
B. E. Christensen, G. Skjåk-Bræk, O. Smidsrød:
Comment on "Conformational changes and aggregation
of alginic acid as determined by fluorescence correlation
spectroscopy", Biomacromolecules 8(10): 3279 (2007)
D. W. Bartlett, M. E. Davis: Physicochemical and
biological characterization of targeted, nucleic acidPhysicochemical and biological
characterization of targeted, nucleic containing nanoparticles, Bioconjugate Chemistry 18(2):
456-468 (2007)
acid-containing nanoparticles
G. E. O. Borgstahl: How to Use Dynamic Light Scattering
to Improve the Likelihood of Growing Macromolecular
How to Use Dynamic Light
Scattering to Improve the Likelihood Crystals, Methods in molecular biology 363: 109-129
of Growing Macromolecular Crystals (2007)
A. V. Gidh, S. R. Decker, C. H. See, M. E. Himmel, C. W.
Characterization of lignin using
Williford: Characterization of lignin using multi-angle laser
multi-angle laser light scattering and light scattering and atomic force microscopy, Analytica
atomic force microscopy
Chimica Acta 555(2):250-258 (2006)
A. Moreno, J. Mas-Oliva, M. Soriano-García, C. O.
Salvador, V. M. Bolaños-García: Turbidity as a useful
Turbidity as a useful optical
optical parameter to predict protein crystallization by
parameter to predict protein
dynamic light scattering, Journal of Molecular Structure
crystallization by dynamic light
519(1-3): 243-256 (2000)
scattering
Fields, G., Alonso, D., Stiger, D., Dill K.: Theory for the
aggregation of proteins and copolymers. J. Phys. Chem.
Theory for the aggregation of
96:3974-3981, 1992
proteins and copolymers
Aggregation of recombinant human Krishnan, S. et al.: Aggregation of recombinant human
interferon gamma: kinetics and
interferon gamma: kinetics and structural transitions. J.
structural transitions
Pharm. Sci. 87: 1069-1076, 1998
Antibody response to aggregated
HermelingS., Schellekens H., Maas C., Gebbink M. F. G.,
human interferon alpha2b in wildCrommelin D. J. A., Jiskoot W.: Antibody response to
type and transgenic immune tolerant aggregated human interferon alpha2b in wild-type and
mice depends on type and level of
transgenic immune tolerant mice depends on type and
aggregation
level of aggregation, JPS 95: 1084-1096 (2006)
4.1 Aggregate/Particle and molecular structure
Data
Source
Substance
Class
In vitro
Protein
Further substance
classification /
Substance name
Corresponding
author / Group
head
Shen
Title
Structure and mechanical properties of
artificial protein hydrogels assembled
through aggregation of leucine zipper
peptide domains
Page 31 of 46
Full citation
W. Shen, J. A. Kornfield, D. A. Tirrell: Structure and
mechanical properties of artificial protein hydrogels
assembled through aggregation of leucine zipper peptide
domains, Soft Matter 3: 99-107 (2007)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro
Protein
Protein
In vitro
alpha-synuclein
alpha-synuclein
Chitosan
In vitro
Dusa
Characterization of oligomers during alphasynuclein aggregation using intrinsic
tryptophan fluorescence
Kaylor
Characterization of oligomeric intermediates
in alpha-synuclein fibrillation: FRET studies
of Y125W/Y133F/Y136F alpha-synuclein
Chen
Effect of the Degree of Deacetylation and
the Substitution of Carboxymethyl Chitosan
on Its Aggregation Behavior
Mozumder
Influence of hydrophobe content and salt
concentration on dilute solution behaviour of
hydrophobically modified ionic polymers
from diallylammonium salts/sulfur dioxide
cyclocopolymerization: light scattering and
fluorescence spectroscopy
In vitro
Protein
β2-microglobulin
Heegaard,
Unfolding, aggregation, and seeded amyloid
formation of lysine-58-cleaved β2microglobulin
In vitro
Protein
fibrinogen
Tsurupa
Do the isolated fibrinogen alphaC-domains
form ordered oligomers?
Kashlan
A comprehensive model for the allosteric
regulation of mammalian ribonucleotide
reductase. Functional consequences of
ATP- and dATP-induced oligomerization of
the large subunit
Riley
Physicochemical evaluation of nanoparticles
assembled from poly(lactic acid)poly(ethylene glycol) (PLA-PEG) block
copolymers as drug delivery vehicles
In vitro
In vitro
Protein
ribonucleotide
reductase
Copolymers
Page 32 of 46
Version 30 July 2010
A. Dusa, J. Kaylor, S. Edridge, N. Bodner, D.-P. Hong, A.
L. Fink: Characterization of oligomers during alphasynuclein aggregation using intrinsic tryptophan
fluorescence, Biochemistry 45(8): 2752-2760 (2006)
J. Kaylor, N. Bodner, S. Edridge, G. Yamin, D.-P. Hong,
A. L. Fink: Characterization of oligomeric intermediates in
alpha-synuclein fibrillation: FRET studies of
Y125W/Y133F/Y136F alpha-synuclein, The Journal of
Molecular Biology 353: 357-372 (2005)
L. Chen, Y. Du, Z. Tian, L. Sun: Effect of the Degree of
Deacetylation and the Substitution of Carboxymethyl
Chitosan on Its Aggregation Behavior, Journal of Polymer
Science: Part B: Polymer Physics, Journal of Polymer
Science: Part B: Polymer Physics 43(3): 296-305 (2005)
M. S. Mozumder, R. S. Alnaizy, Yunusa Umar, Sk. Asrof
Ali, B. F. Abu-Sharkh: Influence of hydrophobe content
and salt concentration on dilute solution behaviour of
hydrophobically modified ionic polymers from
diallylammonium salts/sulfur dioxide
cyclocopolymerization: light scattering and fluorescence
spectroscopy, European Polymer Journal 41(10): 22242231 (2005)
N. H. H. Heegaard, T. J. D. Jørgensen, N. Rozlosnik, D.
B. Corlin, J. S. Pedersen, A. G. Tempesta, P. Roepstorff,
R. Bauer, M. H. Nissen: Unfolding, aggregation, and
seeded amyloid formation of lysine-58-cleaved β2microglobulin, Biochemistry 44: 4397-4407 (2005)
G. Tsurupa, Y. Veklich, R. Hantgan, A. M. Belkin, J. W.
Weisel, L. Medved: Do the isolated fibrinogen alphaCdomains form ordered oligomers?Biophysical Chemistry
112(2-3): 257-266 (2004)
O. B. Kashlan, C. P. Scott, J. D. Lear, B. S. Cooperman:
A comprehensive model for the allosteric regulation of
mammalian ribonucleotide reductase. Functional
consequences of ATP- and dATP-induced
oligomerization of the large subunit, Biochemistry 41(2):
462-474 (2002)
T. Riley, S. Stolnik, C. R. Heald, C. D. Xiong, M. C.
Garnett, L. Illum, S. S. Davis: Physicochemical evaluation
of nanoparticles assembled from poly(lactic acid)poly(ethylene glycol) (PLA-PEG) block copolymers as
drug delivery vehicles, Langmuir 17(11): 3168–3174
(2001)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
surfactants
Okano
In vitro
Protein
CoA transferase
Kay
In vitro
Protein
RANTES
Skelton
In vitro
polystyrene
Zhong
in vitro
ProteinPolysaccharide
Complex
Tao
In vitro
copolymers
Guan
In vitro
Peptid
In vitro
Peptide
Amyloid Abeta (142)
Rambaldi
In vitro,
In vivo
animal
Peptid
Salmon calcitonin
Cheng
In vitro
Sastry
Wang
Fluorescence and light-scattering studies of
the aggregation of cationic surfactants in
aqueous solution: effects of headgroup
structure
Version 30 July 2010
L. T. Okano, F. H. Quina, O. A. El Seoud: Fluorescence
and light-scattering studies of the aggregation of cationic
surfactants in aqueous solution: effects of headgroup
structure, Langmuir 16(7): 3119–3123 (2000)
J. -C. Rochet, K. Oikawa, L. D. Hicks, C. M. Kay, W. A.
Bridger, W. T. Wolodko: Productive interactions between
Productive interactions between the Two
the Two domains of pig heart CoA transferase during
domains of pig heart CoA transferase during folding and assembly, Biochemistry 36(29): 8807-8820
folding and assembly
(1997)
N. J. Skelton, F. Aspiras, J. Ogez, T. J. Schall: Proton
Proton NMR Assignments and Solution
NMR Assignments and Solution Conformation of
Conformation of RANTES, a Chemokine of RANTES, a Chemokine of the C-C Type, Biochemistry
the C-C Type
34(16): 5329-5342 (1995)
X. F. Zhong, A. Eisenberg: Synthesis and
characterization of 1,2-dicarboxyethyl-terminated
Synthesis and characterization of 1,2dicarboxyethyl-terminated polystyrene
polystyrene, Macromolecules 27 (18): 4914–4918 (1994)
Y. Tao, F. Yan, L. Zhang: Fractionation and
Characterization of a Protein-Polysaccharide Complex
Fractionation and Characterization of a
from Pleurotus tuberregium Sclerotia, Journal of Polymer
Protein-Polysaccharide Complex from
Science, Part B: Polymer Physics 45(18): 2546-2554
Pleurotus tuberregium Sclerotia
(2007)
Synthesis and Characterization of
H. Guan, Z. Xie, P. Zhang, C. Deng, X. Chen, X. Jing:
Biodegradable Amphiphilic Triblock
Synthesis and Characterization of Biodegradable
Copolymers Containing L-Glutamic Acid
Amphiphilic Triblock Copolymers Containing L-Glutamic
Units
Acid Units, Biomacromolecules 6(4): 1954-1960 (2005)
S. Sastry, N. Linderoth: Molecular Mechanisms of
Molecular Mechanisms of Peptide Loading
Peptide Loading by the Tumor Rejection Antigen/Heat
by the Tumor Rejection Antigen/Heat Shock Shock Chaperone gp96 (GRP94), The Journal of
Chaperone gp96 (GRP94)
Biological Chemistry 274(17): 12023-12035 (1999)
D. C. Rambaldi, A. Zattoni, P. Reschiglian, R. Colombo,
E. De Lorenzi: In vitro amyloid Aß1-42 peptide
In vitro amyloid Aß1-42 peptide aggregation aggregation monitoring by asymmetrical flow field-flow
monitoring by asymmetrical flow field-flow
fractionation with multi-angle light scattering detection,
fractionation with multi-angle light scattering Analytica Bioanalytical Chemistry 394(8): 2145-2149
detection
(2009)
W. Cheng, L.-Y. Lim: Synthesis, Characterization and In
Vivo Activity of Salmon Calcitonin Coconjugated With
Synthesis, Characterization and In Vivo
Activity of Salmon Calcitonin Coconjugated Lipid and Polyethylene Glycol, Journal of Pharmaceutical
Science 98(4): 1438-1451 (2009)
With Lipid and Polyethylene Glycol
Amphiphilic Diblock Copolymers
D. Wang, H. Ren, X. Wang, X. Wang: Amphiphilic Diblock
Functionalized with Strong Push-Pull Azo
Copolymers Functionalized with Strong Push-Pull Azo
Chromophores: Synthesis and MultiChromophores: Synthesis and Multi-Morphological
Morphological Aggregation
Aggregation, Macromolecules 41 (23) : 9382-9388 (2008)
Page 33 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Peptid
Gordon
Structural and functional properties of
peptides based on the N-terminus of HIV-1
gp41 and the C-terminus of the amyloidbeta protein
In vitro
Protein
STIM1, STIM2
Zheng
Biophysical characterization of the EF-hand
and SAM domain containing Ca2+ sensory
region of STIM1 and STIM2
In vitro
Protein
DegP
Krojer
Structural basis for the regulated protease
and chaperone function of DegP
Takata
Deamidation destabilizes and triggers
aggregation of a lens protein, betaA3crystallin
In vitro
Protein
betaA3-crystallin
In vitro
MTAC-BA-AM
Cao
Aggregation Behavior of Cationic
Copolymer Methacryloxyethyl Trimethyl
Ammonium Chloride-Butyl AcrylateAcrylamide in Aqueous Solution
In vitro
sodium alginat,
curcubit[6] uril
Huang
Aggregation behavior of sodium alginate
with cucurbit[6]uril in aqueous solution
alphaB-crystallin
Ecroyd
Mimicking phosphorylation of alphaBcrystallin affects its chaperone activity
Zanier
Formation of well-defined soluble
aggregates upon fusion to MBP is a generic
property of E6 proteins from various human
papillomavirus species
In vitro
In vitro
Protein
Protein
E6 oncoprotein
Page 34 of 46
Version 30 July 2010
L. M. Gordon, A. Nisthal, A. B. Lee, S. Eskandari, P.
Ruchala, C.-L. Jung, A. J. Waring, P. W. Mobley:
Structural and functional properties of peptides based on
the N-terminus of HIV-1 gp41 and the C-terminus of the
amyloid-beta protein, Biochimica et Biophysica Acta
1778(10): 2127-2137 (2008)
L. Zheng, P. B. Stathopulos, G.-Y. Li, M. Ikura:
Biophysical characterization of the EF-hand and SAM
domain containing Ca2+ sensory region of STIM1 and
STIM2, Biochemical and Biophysical Research
Communications 369: 240-246 (2008)
T. Krojer, J. Sawa, E. Schäfer, H. R. Saibil, M. Ehrmann,
T. Clausen: Structural basis for the regulated protease
and chaperone function of DegP, Nature 453: 885-890
(2008)
T. Takata, J. T. Oxford, B. Demeler, K. J. Lampi:
Deamidation destabilizes and triggers aggregation of a
lens protein, betaA3-crystallin, Protein Science 17(9):
1565-1575 (2008)
X. Cao, Y. Tan, G. Xu, D. Wu: Aggregation Behavior of
Cationic Copolymer Methacryloxyethyl Trimethyl
Ammonium Chloride-Butyl Acrylate-Acrylamide in
Aqueous Solution, Journal of Dispersion Science and
Technology 29(1): 70-76 (2008)
X. Huang, Y. Tan, Q. Zhou, Y. Wang, Y. Che:
Aggregation behavior of sodium alginate with
cucurbit[6]uril in aqueous solution, Carbohydrate
Polymers 74(3): 685-690 (2008)
H. Ecroyd, S. Meehan, J. Horwitz, J.A. Aquilana, J.L.P.
Benesche, C.V. Robinson, C.E. Macphee, J.A. Carver:
Mimicking phosphorylation of alphaB-crystallin affects its
chaperone activity, Biochemistry Journal 401: 129-141
(2007)
K. Zanier, Y. Nominé, S. Charbonnier, C. Ruhlmann, P.
Schultz, J. Schweizer, G. Travé: Formation of welldefined soluble aggregates upon fusion to MBP is a
generic property of E6 proteins from various human
papillomavirus species, Protein Expression and
Purification 51(1): 59-70 (2007)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
superoxid
dismutase
Metal-free superoxide dismutase forms
soluble oligomers under physiological
conditions: A possible general mechanism
for familial ALS
Banci
Version 30 July 2010
L. Banci, I. Bertini, A. Durazo, S. Girotto, E. Butler Gralla,
M. Martinelli, J. Selverstone Valentine, M. Vieru, J.P.
Whitelegge: Metal-free superoxide dismutase forms
soluble oligomers under physiological conditions: A
possible general mechanism for familial ALS, Biophysics
PNAS 104 (27): 11263-11267 (2007)
4.2 Aggregate/Particle and long-term storage
Data Source
No
experimental
data
Substance
Class
Further substance
classification /
Substance name
Protein
Corresponding
author / Group head
0 Arakawa T.
Title
Factors affecting shortterm and long-term
stabilities of proteins
Full citation
Arakawa T., Prestrelski S.J., Kenney W.C., Carpenter
J.F.: Factors affecting short-term and long-term stabilities
of proteins, Adv. Drug Deliv. Rev. 10: 1-28, 1993
4.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
Substance
Class
Further substance
classification /
Substance name
In vitro
Protein
bovine carbonic
anhydrase
Yan
In vitro
Protein
Maltose-bindingprotein
Huang
In vitro
Azobenzene
Li
In vitro
Protein
mouse prion protein
Vendrely
I
In vitro
Protein
beta-lactoglobulin
Data
Source
Corresponding
author / Group
head
Zhu
Title
Fabrication of single carbonic
anhydrase nanogel against
denaturation and aggregation at high
temperature
Induced fit of passenger proteins fused
to Archaea maltose binding proteins
Formation of photoresponsive uniform
colloidal spheres from an amphiphilic
azobenzene-containing random
copolymer
Assembly of the full-length recombinant
mouse prion protein I. Formation of
soluble oligomers
Studying Protein Aggregation by
Programmed Flow Field-Flow
Fractionation Using Ceramic Hollow
Fibers
Page 35 of 46
Full citation
M. Yan, Z. Liu, D. Lu, Z. Liu: Fabrication of single carbonic
anhydrase nanogel against denaturation and aggregation at
high temperature, Biomacromolecules 8(2): 560-565 (2007)
H. Huang, J. Liu, A. de Marco: Induced fit of passenger
proteins fused to Archaea maltose binding proteins,
Biochemical and Biophysical Research Communications
344(1): 25-29 (2006)
Y. Li, Y. Deng, X. Tong, X. Wang: Formation of
photoresponsive uniform colloidal spheres from an
amphiphilic azobenzene-containing random copolymer,
Macromolecules 39(3): 1108-1115 (2006)
C. Vendrely, H. Valadié, L. Bednarova, L. Cardin, M.
Pasdeloup, J. Cappadoro, J. Bednar, M. Rinaudo, M. Jamin:
Assembly of the full-length recombinant mouse prion protein
I. Formation of soluble oligomers, Biochimica et Biophysica
Acta 1724(3): 355-366 (2005)
R. Zhu, W. Frankema, Y. Huo, W. Th. Kok: Studying Protein
Aggregation by Programmed Flow Field-Flow Fractionation
Using Ceramic Hollow Fibers, Analytical Chemistry 77(14):
4581-4586 (2005)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
In vitro
In vitro
Protein
In vitro
In vitro
In vitro
Berg
Cooperative binding of monodisperse
anionic amphiphiles to the i-face:
phospholipase A2-paradigm for
interfacial binding
poly(vinyl alcohol)
Sho
SEC-MALS characterization of
aggregation behavior of poly(vinyl
alcohol) in water
actose whey
Mleko
copolymer
Pispas
phospholipase A2
Protein
In vitro
Fraunhofer
Photon correlation spectroscopy
investigations of proteins
Aymmetrical Flow Field-Flow
Fractionation in Pharmaceutical
Analytics: Investigations in Aggregation
Tendencies of Pharmaceutical
Antibodies
GonzálezGaitano
The aggregation of cyclodextrins as
studied by photon correlation
spectroscopy
Star-shaped poly(ethylene glycol)block-polyethylenimine copolymers
enhance DNA condensation of low
molecular weight polyethylenimines
Gun’ko
Antibody
cyclodextrin
Rheological properties of reduced
lactose whey dispersions
Micellization behavior of
poly(butadiene-b-sodium methacrylate)
copolymers in dilute aqueous media
In vitro
copolymers
Petersen
In vitro
copolymers
Sotiriou
In vitro
liposomes, latex
Wang
Micellization behavior of PS(PI)3
miktoarm star copolymers
Aggregation rate measurements by
zero-angle time-resolved multiangle
laser light scattering
de la Fuente
Process-induced changes in whey
proteins during the maufacture of whey
protein concentrates
In vitro
Protein
Whey Protein
Page 36 of 46
Version 30 July 2010
O. G. Berg, B.-Z. Yu, C. Chang, K. A. Koehler, M. K. Jain:
Cooperative binding of monodisperse anionic amphiphiles to
the i-face: phospholipase A2-paradigm for interfacial binding,
Biochemistry 43(25): 7999-8013 (2004)
K. Sho, S. Kawaguchi: SEC-MALS characterization of
aggregation behavior of poly(vinyl alcohol) in water,
Japanese Journal of Polymer Science and Technology
60(6): 300-304 (2003)
S. Mleko, P. Janas, T. Wang, J. A. Lucey: Rheological
properties of reduced lactose whey dispersions, Int Journal
of Dairy Technology 56(3): 157-161 (2003)
S. Pispas, N. Hadjichristidis: Micellization behavior of
poly(butadiene-b-sodium methacrylate) copolymers in dilute
aqueous media, Macromolecules 36 (23): 8732-8737 (2003)
V. M. Gun’ko, A. V. Klyueva, Y. N. Levchuk, R. Leboda:
Photon correlation spectroscopy investigations of proteins,
Advances in Colloid and Interface Science 105(1-3): 201328
Thesis: W. Fraunhofer: Aymmetrical Flow Field-Flow
Fractionation in Pharmaceutical Analytics: Investigations in
Aggregation Tendencies of Pharmaceutical Antibodies
(2003)
G. González-Gaitano, P. Rodríguez, J. R. Isasi, M. Fuentes,
G. Tardajos, M. Sánchez: The aggregation of cyclodextrins
as studied by photon correlation spectroscopy, Journal of
Inclusion Phenomena and Macrocyclic Chemistry 44: 101105 (2002)
H. Petersen, K. Kunath, A. L. Martin, S. Stolnik, C. J.
Roberts, M. C. Davies, T. Kissel: Star-shaped poly(ethylene
glycol)- block-polyethylenimine copolymers enhance DNA
condensation of low molecular weight polyethylenimines,
Biomacromolecules 3(5): 926-936 (2002)
K. Sotiriou, A. Nannou, G. Velis, S. Pispas: Micellization
behavior of PS(PI)3 miktoarm star copolymers,
Macromolecules 35(10): 4106-4112 (2002)
K. Wang, A. K. Singh, J. H. van Zanten: Aggregation rate
measurements by zero-angle time-resolved multiangle laser
light scattering, Langmuir 18(6): 2421-2425 (2002)
M. A. de la Fuente, Y. Hemar, M. Tamehana, P. A. Munro,
H. Singh: Process-induced changes in whey proteins during
the maufacture of whey protein concentrates, International
Dairy Journal 12(4): 361-369 (2002)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Protein
In vitro
Prefoldin
Okochi
Aeromonas Gum
Zhang
In vitro
Protein
dried egg white
Handa
In vitro
Protein
Apoferritin
Petsev
In vitro
Clostridium difficile
toxins
Palace
In vitro
pectin
Fishman
In vitro
Protein
beta-lactoglobulin
Ugolini
In vitro
Protein
Apoferritin
Petsev
In vitro
Erwinia gum
In vitro
polyvinyl chloride,
dioxane
Hong
In vitro
ionic dyestuff
Inglés
Version 30 July 2010
M. Okochi, T. Yoshida, T. Maruyama, Y. Kawarabayasi, H.
Kikuchi, M. Yohda: Pyrococcus prefoldin stabilizes proteinPyrococcus prefoldin stabilizes protein- folding intermediates and transfers them to chaperonins for
folding intermediates and transfers
correct folding, Biochemical and Biophysical Research
them to chaperonins for correct folding
Communications 291(4): 769-774 (2002)
X. Xu, L. Zhang, T. Norisuye: Molecular Weight and
Molecular Weight and Aggregation of
Aggregation of Aeromonas Gum Treated with Dimethyl
Aeromonas Gum Treated with Dimethyl Sulfoxide in Aqueous Solution, Journal of Polymer Science:
Sulfoxide in Aqueous Solution
Part B: Polymer Physics 40(19): 2269-2276 (2002)
A. Handa, K. Hayashi, H. Shidara, N. Kuroda: Correlation of
Correlation of the protein structure and the protein structure and gelling properties in dried egg white
products, Journal of Agricultural and Food Chemistry 49(8):
gelling properties in dried egg white
products
3957-3964 (2002)
D. N. Petsev, B. R. Thomas, S.-T. Yau, D. Tsekova, C.
Nanev, W. W. Wilson, P. G. Vekilov: TemperatureTemperature-independent solubility and independent solubility and interactions between apoferritin
interactions between apoferritin
monomers and dimers in solution, Journal of Crystal Growth
monomers and dimers in solution
232(1-4): 21-29 (2001)
Analysis of the physiochemical
G. P. Palace, P. Lazari, K. Norton: Analysis of the
interactions between Clostridium difficile physiochemical interactions between Clostridium difficile
toxins and cholestyramine using liquid
toxins and cholestyramine using liquid chromatography with
chromatography with post-column
post-column derivatization, Biochimica et Biophysica Acta
derivatization
1546(1): 171-184 (2001)
M. L. Fishman, H. K. Chau, F. Kolpak, J. Brady: Solvent
effects on the molecular properties of pectins, Journal of
Solvent effects on the molecular
Agricultural and Food Chemistry 49(9): 4494-4501 (2001)
properties of pectins
R. Ugolini, L. Ragona, E. Silletti, F. Fogolari, R. W.
Visschers, A. C. Alting, H. Molinari: Dimerization, stability
Dimerization, stability and electrostatic
and electrostatic properties of porcine beta-lactoglobulin,
properties of porcine beta-lactoglobulin Euopean Journal of Biochemistry 268(16): 4477-4488
D. N. Petsev, B. R. Thomas, S.-T. Yasu, P. G. Vekilov:
Interactions and aggregation of
Interactions and aggregation of apoferritin molecules in
apoferritin molecules in solution: effects solution: effects of added electrolytes, Biophysical Journal
of added electrolytes
78(4): 2060-2069 (2000)
L. Zhang, X. Xu, S. Pan: Effects of the thermal history and
concentration on the aggregation of erwinia gum in aqueous
Effects of the thermal history and
solution, Journal of Polymer Science: Part B: Polymer
concentration on the aggregation of
erwinia gum in aqueous solution
Physics 38(10): 1352 - 1358 (2000)
Light scattering studies on aggregation P.-D. Hong, C.-M. Chou, J.-H. Chen: Light scattering studies
behavior of polyvinyl chloride/dioxane
on aggregation behavior of polyvinyl chloride/dioxane
solutions
solutions, Polymer 41(15): 5847-5854 (2000)
Time-resolved recording of ionic
S. E. Inglés, A. Katzenstein, W. Schlenker, K. Huber: Timedyestuff aggregation by static light
resolved recording of ionic dyestuff aggregation by static
scattering
light scattering, Langmuir 16 (7): 3010–3018 (2000)
Page 37 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
On the interchain associations in
aqueous solutions of a succinoglycan
polysaccharide
In vitro
Succinoglycan
Boutebba
In vitro
Erwinia gum
Zhang
In vitro
K-carrageenan
Wittgren
Rheological behavior of erwinia gum in
aqueous solution
Conformational change and
aggregation of K-carrageenan studied
by flow field-flow fractionation and
multiangle light scattering
Bossé
Aggregation behaviour below the
gelation threshold for metal-olefin
coordination in diene polymers
In vitro
diene polymers
in vitro
block polyelectrolyte Khougaz
Micellization in block polyelectrolyte
solutions. 3. Static light scattering
characterization
In vitro
poly(1,3-dioxolane)
Benkhira
Conformation of poly(1,3-dioxolane) in
dilute and semidilute aqueous solutions
In vitro
heparin
Mach
Nature of the interaction of heparin with
acidic fibroblast growth factor
Hoppe
Characterization of Purified Antibody
Dimers
A high throughput dimer screening
assay for monoclonal antibodies using
chemical cross-linking and microchip
electrophoresis
Characterization of seed nuclei in
glucagon aggregation using light
scattering methods and field-flow
fractionation
Kheirandish
Shear and elongational flow behavior of
acrylic thickener solutions Part I: Effect
of intermolecular aggregation
Demeule
Characterization of protein aggregation:
the case of a therapeutic
immunoglobulin
In vitro
Antibody
Moll
In vitro
Antibody
Chen
In vitro
Peptid
Glucagon
In vitro
In vitro
Antibody
IgA
Page 38 of 46
Version 30 July 2010
A. Boutebba, M. Milas, M. Rinaudo: On the interchain
associations in aqueous solutions of a succinoglycan
polysaccharide, International Journal of Biological
Macromolecules 24(4): 319-327 (1999)
L. Zhang, M. Zhang, J. Chen, H. Iijima, H. Tsuchiya:
Rheological behavior of erwinia gum in aqueous solution,
Chinese Journal of Polymer Science 17(6): 557-561 (1999)
B. Wittgren, J. Borgstron, L. Piculell, K. -G. Wahlund:
Conformational change and aggregation of K-carrageenan
studied by flow field-flow fractionation and multiangle light
scattering, Biopolymers 45(1): 85-96 (1998)
F. Bossé, P. Das, L. A. Belfiore: Aggregation behaviour
below the gelation threshold for metal-olefin coordination in
diene polymers, Polymer Gels and Networks 5(5): 387-413
(1997)
K. Khougaz, I. Astafieva, A. Eisenberg: Micellization in block
polyelectrolyte solutions. 3. Static light scattering
characterization, Macromolecules 28 (21): 7135–7147
(1995)
A. Benkhira, E. Franta, M. Rawiso, J. Fracois: Conformation
of poly(1,3-dioxolane) in dilute and semidilute aqueous
solutions, Macromolecules 27 (14): 3963–3972 (1994)
H. Mach, D. B. Volkin, C. J. Burke, C. R. Middaugh: Nature
of the interaction of heparin with acidic fibroblast growth
factor, Biochemistry 32(20): 5480-5489 (1993)
Poster: J. R. Moll, V. Miranda, Y.-M. Li, L. Bergerud, T. M.
Spitznagel, M. P. Byrne: Characterization of Purified
Antibody Dimers (2006)
X. Chen, G. C. Flynn: A high throughput dimer screening
assay for monoclonal antibodies using chemical crosslinking and microchip electrophoresis, Journal of
Chromatography B 877(27): 3012-3018 (2009)
C. C. Hoppe, L. T. Nguyen, L. E. Kirsch, J. M. Wiencek:
Characterization of seed nuclei in glucagon aggregation
using light scattering methods and field-flow fractionation,
Journal of Biological Engineering 2:10 (2008)
S. Kheirandish, I. Guybaidullin, W. Wohlleben, N.
Willenbacher: Shear and elongational flow behavior of
acrylic thickener solutions Part I: Effect of intermolecular
aggregation, Rheologica Acta 47(9): 999-1013 (2008)
B. Demeule, M. J. Lawrence, A. F. Drake, R. Gurny, T.
Arvinte: Characterization of protein aggregation: the case of
a therapeutic immunoglobulin, Biochimica et Biophysica
Acta 1774(1): 146-153 (2007)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
Antibody
In vitro
Gabrielson
poly(1,3cyclohexadiene)
Natori
lumazine synthase
Neumaier
In vitro
Protein
In vitro
Protein
0 Manning M.C
Please
select
Protein
0 Chi E.Y.
Version 30 July 2010
J. P. Gabrielson, M. L. Brader, A. H. Pekar, K. B. Mathis, G.
Winter, J. F. Carpenter, T. W. Randolph: Quantitation of
Aggregate Levels in a Recombinant Humanized Monoclonal
Antibody Formulation by Size-Exclusion Chromatography,
Asymmetrical Flow Field-Flow Fractionation, and
Sedimentation Velocity, Journal of Pharmaceutical Sciences
96(2): 268-279 (2007)
I. Natori, H. Sato: Aggregation of poly(1,3-cyclohexadiene):
Aggregation of poly(1,3effects of molecular weight and polymer chain structure,
Journal of Polymer Science Part B: Polymer Physics 44:
cyclohexadiene): effects of molecular
weight and polymer chain structure
1442-1452 (2006)
Early stages of crystallization of
Thesis: N. Neumaier: Early stages of crystallization of
lumazine synthase from Bacillus subtilis lumazine synthase from Bacillus subtilis (2005)
Manning M.C., Patel K., Borchhardt R.: Stability of Protein
Pharmaceuticals. Pharm. Res. 6: 903-918 (1989)
Stability of Protein Pharmaceuticals
Chi E.Y., Krishnan S., Randolph T.W. and Carpenter J.F.:
Physical Stability of Proteins in aqueous Solution:
Physical Stability of Proteins in aqueous Mechanism and Driving Forces in Nonnative protein
Solution: Mechanism and Driving
aggregation, Pharm Research, Vol. 20, No. 9: 1325-1336
Forces in Nonnative protein aggregation (2003)
Quantitation of Aggregate Levels in a
Recombinant Humanized Monoclonal
Antibody Formulation by Size-Exclusion
Chromatography, Asymmetrical Flow
Field-Flow Fractionation, and
Sedimentation Velocity
4.4 Immunogenicity observation - acute and/or sporadic
Data
Source
Substance
Class
In vitro
Further substance
classification /
Substance name
Corresponding
author / Group
head
copolymers
Petersen
Title
Synthesis, characterization, and
biocompatibility of polyethyleniminegraft-poly(ethylene glycol) block
copolymers
Full citation
H. Petersen, P. M. Fechner, D. Fischer, T. Kissel:
Synthesis, characterization, and biocompatibility of
polyethylenimine-graft-poly(ethylene glycol) block
copolymers, Macromolecules 35(18): 6867-6874 (2002)
4.5 Immunogenicity observation - chronic and/or general
N/A
4.6 Immunogenicity assays
Data
Source
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
Title
Full citation
Page 39 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vitro
In vitro,
In vivo
animal
Peptide
In vitro,
In vivo
animal
In vitro,
In vivo
animal
Protein
streptococcal
pyrogenic
exotoxins
Proft
Bacillus anthracis
Joyce
capsular
polysaccharides
Jin
gp 41
Qiao
Version 30 July 2010
T. Proft, V. L. Arcus, V. Handley, E. N. Baker, J. D. Fraser:
Immunological and biochemical characterization of
streptococcal pyrogenic exotoxins I and J (SPE-I and SPEJ) from Streptococcus pyogenes, Journal of Immunology
166(11): 6711-6719 (2001)
J. Joyce, J. Cook, D. Chabot, R. Hepler, W. Shoop, Q. Xu,
T. Stambaugh, M. Aste-Amezaga, S. Wang, L. Indrawati,
M. Bruner, A. Friedlander, P. Keller, M. Caulfield:
Immunogenicity and protective efficacy
Immunogenicity and protective efficacy of Bacillus
anthracis poly-gamma-D-glutamic acid capsule covalently
of Bacillus anthracis poly-gamma-Dglutamic acid capsule covalently coupled coupled to a protein carrier using a novel triazine-based
to a protein carrier using a novel triazine- conjugation strategy, The Journal of Biological Chemistry
281(8): 4831-4843 (2005)
based conjugation strategy
Z. Jin, G. A. Bohach, J. Shiloach, S. E. Norris, D. I.
Conjugates of Group A and W135
Freedberg, C. Deobald, B. Coxon, J. B. Robbins, R.
Schneerson: Conjugates of Group A and W135 capsular
capsular polysaccharides of neisseria
meningitidis bound to recombinant
polysaccharides of neisseria meningitidis bound to
recombinant staphylococcus aureus enterotoxin c1:
staphylococcus aureus enterotoxin c1:
preparation, physicochemical
preparation, physicochemical characterization, and
immunological properties in mice, Infection and Immunity
characterization, and immunological
properties in mice
73(12): 7887-7893 (2005)
Z.-S. Qiao, M. Kim, B. Reinhold, D. Montefiori, J. Wang, E.
Design, Expression, and Immunogenicity L. Reinherz: Design, Expression, and Immunogenicity of a
Soluble HIV Trimeric Envelope Fragment Adopting a
of a Soluble HIV Trimeric Envelope
Fragment Adopting a Prefusion
Prefusion gp41Configuration, The Journal of Biological
Chemistry 20(24): 23138-23146 (2005)
gp41Configuration
Immunological and biochemical
characterization of streptococcal
pyrogenic exotoxins I and J (SPE-I and
SPE-J) from Streptococcus pyogenes
Page 40 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
5 Immunogenicity observation - acute and/or sporadic
5.1 Aggregate/Particle and molecular structure
Data
Source
In vitro
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
Nano-carriers
Steele
Title
Dendrimeric Alkylated Polyethylenimine
Nano-carriers with Acid-Cleavable Outer
Cationic Shells Mediate Improved
Transfection Efficiency Without Increasing
Toxicity
Full citation
T. W. J. Steele, W. T. Shier: Dendrimeric Alkylated
Polyethylenimine Nano-carriers with Acid-Cleavable
Outer Cationic Shells Mediate Improved Transfection
Efficiency Without Increasing Toxicity, Pharmaceutical
Research 27(4): 683-698 (2010)
5.2 Aggregate/Particle and long-term storage
N/A
5.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
N/A
5.4 Aggregate/Particle detection/characterization
N/A
5.5 Immunogenicity observation - chronic and/or general
N/A
5.6 Immunogenicity assays
N/A
Page 41 of 46
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
6 Immunogenicity observation - chronic and/or general
6.1 Aggregate/Particle and molecular structure
Data Source
No
experimental
data
Substance
Class
Further substance
classification /
Substance name
Antibody
therapeutic proteins
Corresponding
author / Group head Title
Structure-immunogenicity
realtionships of therapeutic
Hermeling Suzanne proteins
Full citation
Hermeling S., Crommelin D. J. A., Schellekens H., Jiskoot
W.: Structure-immunogenicity realtionships of therapeutic
proteins, Pharmaceutical Research 21: 897-903 (2004)
6.2 Aggregate/Particle and long-term storage
N/A
6.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
N/A
6.4 Aggregate/Particle detection/characterization
Data
Source
In vitro
In vivo
animal
Substance
Class
Antibody
Protein
Further substance
classification /
Substance name
Ig
Interferon Alpha
Corresponding
author / Group
head
Title
Kafi
Maleimide conjugation markedly
enhances the immunogenicity of both
human and murine idiotype-KLH
vaccines
Braun Andrea
Protein aggregates seem to play a key
role among the parameters influencing
the antigenicity of interferon alpha in
normal and transgenis mice
6.5 Immunogenicity observation - acute and/or sporadic
N/A
Page 42 of 46
Full citation
K. Kafi, D. J. Betting, R. E. Yamada, M. Bacica, K. K.
Steward, J. M. Timmerman: Maleimide conjugation
markedly enhances the immunogenicity of both human
and murine idiotype-KLH vaccines, Molecular Immunology
46(3): 448-456 (2009)
Braun A., Kwee L., Labow M. A. and Alsenz J.:Protein
aggregates seem to play a key role among the parameters
influencing the antigenicity of interferon alpha in normal
and transgenis mice, Pharmaceutical Research 14: 14721478 (1997)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
6.6 Immunogenicity assays
N/A
Page 43 of 46
Version 30 July 2010
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
7 Immunogenicity assays
Data
Source
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
In vitro
Protein
Melan-A/MART-1
Adamina
Title
Full citation
M. Adamina, M. Bolli, F. Albo, A. Cavazza, P. Zajac, E. Padovan,
Encapsulation into sterically
R. Schumacher, A. Reschner, C. Feder, W. R. Marti, D. Oertli, M.
Heberer, G. C. Spagnoli: Encapsulation into sterically stabilised
stabilised liposomes enhances
the immunogenicity of melanoma- liposomes enhances the immunogenicity of melanoma-associated
Melan-A/MART-1 epitopes, British Journal of Cancer 90(1): 263associated Melan-A/MART-1
epitopes
269 (2004)
7.1 Aggregate/Particle and molecular structure
Data
Source
Substance
Class
In vitro
Further substance
classification /
Substance name
Corresponding
author / Group
head
Poly(amido amine)s
Wang
Title
Synthesis and Gene Delivery
of Poly(amido amine)s with
Different Branched
Architecture
Full citation
R. Wang, L. Zhou, Y. Zhou, G. Li, X. Zhu, H. Gu, X. Jiang, H. Li, J.
Wu, L. He, X. Guo, B. Zhu, D. Yan: Synthesis and Gene Delivery of
Poly(amido amine)s with Different Branched Architecture,
Biomacromolecules 11(2): 489-495 (2010)
7.2 Aggregate/Particle and long-term storage
N/A
7.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t
Data
Source
In vivo
animal
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group head Title
Protein
human growth
hormone
Amber Haynes
Fradkin
Immunogenicity of aggregates of
recombinant human growth
hormone in mouse models
Page 44 of 46
Full citation
Fradkin A. H., Carpenter J. F., Randolph T. W.:
Immunogenicity of aggregates of recombinant human
growth hormone in mouse models, JPS 98: 3247-3264
(2009)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
Version 30 July 2010
7.4 Aggregate/Particle detection/characterization
Data
Source
Substance
Class
Further substance
classification /
Substance name
Corresponding
author / Group
head
In vitro
Protein
Hemagglutinin
Wei
In vivo
animal
Protein
Plasmodium
falciparum proteins Qian
In vitro
Antibody
anti-p185HER-2
In vitro,
In vivo
animal
Peptid
Kubetzko
Li
Title
Comparative Efficacy of
Neutralizing Antibodies Elicited by
Recombinant Hemagglutinin
Proteins from Avian H5N1
Influenza Virus
Full citation
C.-J. Wei, L. Xu, W.-P. Kong, W. Shi, K. Canis, J. Stevens, Z.-Y.
Yang, A. Dell, S. M. Haslam, I. A. Wilson, G. J. Nabel:
Comparative Efficacy of Neutralizing Antibodies Elicited by
Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza
Virus, Journal of Virology 82(13): 6200-6208 (2008)
F. Qian, Y. Wu, O. Muratova, H. Zhou, G. Dobrescu, P. Duggan,
Conjugating recombinant proteins L. Lynn, G. Song, Y. Zhang, K. Reiter, N. MacDonald, D. L.
Narum, C. A. Long, L. H. Miller, A. Saul, G. E. D. Mullen:
to Pseudomonas aeruginosa
ExoProtein A: A strategy for
Conjugating recombinant proteins to Pseudomonas aeruginosa
ExoProtein A: A strategy for enhancing immunogenicity of
enhancing immunogenicity of
malaria vaccine candidates
malaria vaccine candidates, Vaccine 25(20): 3923-3933 (2007)
Protein PEGylation decreases
S. Kubetzko, C. A. Sarkar, A. Plueckthun: Protein PEGylation
observed target association rates decreases observed target association rates via a dual blocking
via a dual blocking mechanism
mechanism, Molecular Pharmacology 68: 1439-1454 (2005)
S. W. Li, J. Zhang, Y. M. Li, S. H. Ou, G. Y. Huang, Z. Q. He, S.
A bacterially expressed particulate X. Ge, Y. L. Xian, S. Q. Pang, M. H. Ng, N. S. Xia: A bacterially
hepatitis E vaccine: antigenicity,
expressed particulate hepatitis E vaccine: antigenicity,
immunogenicity and protectivity on primates, Vaccine 23(22):
immunogenicity and protectivity
on primates
2893-2901 (2005)
7.5 Immunogenicity observation - acute and/or sporadic
N/A
7.6 Immunogenicity observation - chronic and/or general
Data Source
In vivo animal
No
experimental
data
Substance
Class
Further substance
Corresponding
classification / Substance author / Group
name
head
Title
Protein
Protein therapeutics
Coen Maas
Protein
Biopharmaceuticals
Huub Schellekens
A Role for Protein Misfolding in
immunogenicity of
Biopharmaceuticals
Bioequivalence and the
immunogenicty of
biopharmaceuticals
Page 45 of 46
Full citation
Maas C.,Hermeling s., Bouma B., Jiskoot W., Gebbink
M. F. G.: A Role for Protein Misfolding in
immunogenicity of Biopharmaceuticals, JBC Papers
282:2229-2236 (2006)
Huub Schellekens:Bioequivalence and the
immunogenicty of biopharmaceuticals, Nature Reviews
1:457-462 (2002)
AAPS Focus Group Aggregation and Biological Consequences Literature Collection
In vivo animal
Please
select
Polymere
Dintzis H. M.
Version 30 July 2010
Dintzis H. M., Dintzis R. Z., Vogelstein B.: Molecular
Molecular determinants of
determinants of immunogenicity: The immunonn model
immunogenicity: The immunonn of immune response, Proc, Natl. Acad. Sci. 73:3671model of immune response
3675 (1976)
Page 46 of 46