Table Of ContentSELF-ASSEMBLING PEPTIDE SYSTEMS IN BIOLOGY,
MEDICINE AND ENGINEERING
SELF-ASSEMBLING
PEPTIDE SYSTEMS IN
BIOLOGY, MEDICINE AND
ENGINEERING
editedby
AMALIA AGGELI
NEVILLE BODEN
University ofLeeds,United Kingdom
and
SHUGUANGZHANG
Massachusetts Institute of Technology,
Cambridge,MA,U.S.A.
KLUWER ACADEMIC PUBLISHERS
NEW YORK / BOSTON / DORDRECHT / LONDON / MOSCOW
eBook ISBN: 0-306-46890-5
Print ISBN: 0-792-37090-2
©2002 Kluwer Academic Publishers
New York, Boston, Dordrecht, London, Moscow
Print ©2000 Kluwer Academic Publishers
Dordrecht
All rights reserved
No part of this eBook may be reproduced or transmitted in any form or by any means, electronic,
mechanical, recording, or otherwise, without written consent from the Publisher
Created in the United States of America
Visit Kluwer Online at: http://kluweronline.com
and Kluwer's eBookstore at: http://ebooks.kluweronline.com
TABLEOFCONTENTS
Self-assemblingpeptidesystemsinbiologymedicineandengineering
Foreword xi
Chapter 1
ExploitingPeptideSelf-assemblytoEngineerNovelBiopolymers:Tapes,Ribbons,
FibrilsandFibres 1
A.Aggeli,I.A.Nyrkova,M.Bell,L.Carrick,T.C.B.McLeish,A.N.Semenovand
N.Boden
1.1. Abstract 1
1.2. Introduction 1
1.3. MaterialsandMethods 2
1.4. ResultsandDiscussion 4
Acknowledgements 16
References 16
Chapter 2
Ribbon-likeLamellarStructuresfromChain-foldedPolypeptides 19
E.D.T. Atkins
2.1. IntroductionandBackground 19
2.2. Choice of Poly(Ag)EG Sequence 20
x
2.3 Antiparallelβ -sheetStructuresfoundinSilks 20
2.4. X-rayDiffractionResults 22
2.5. Structure of Poly(AG)EG Crystals 24
3
2.6. PhaseRelationshipbetweenSequenceandFolding 26
2.7. Effect of Animo Acid Side-chain Volume on Sheet Stacking 28
2.8. Whyγ -foldsintheseChain-foldedStructures? 30
2.9. Conclusions 32
Acknowledgements 32
References 33
Chapter 3
Designof Self-assembling PeptidesasCatalystMimetics Using Synthetic
Combinatorial Libraries 35
S.E. Blondelle, E. Crooks,N. ReixachandE. P.Pérez-Payá
3.1. Introduction 35
3.2. Secondary Structure Optimization 36
3.3. Hydrophobic Core Optimization 39
3.4. Identification ofCatalytic Mimetics 41
3.5. Conclusion 43
References 44
vi
Chapter 4
Thermodynamics ofProtein-Protein and Peptide Interactions 47
A. Cooper
4.1. Summary 47
4.2. Introduction 48
4.3. Thermodynamics and Microcalorimetry 48
4.4. Enthalpy-Entropy Compensation 57
4.5. Acknowledgements 64
4.6. References 64
Chapter 5
The Mechanism of Amyloid Formation and its Links to Human Disease and
Biological Evolution 65
C.M. Dobson
Protein misfolding is linked to disease 65
Soluble proteins convert into aggregates under denaturing conditions 66
Amyloid is ageneric structural form ofproteins 67
Living systems avoid forming amyloid 69
New insights into evolutionarybiology? 70
OpportunitiesfortheFuture 71
Acknowledgements 72
References 73
Chapter6
Transgenic Plants forLarge Scale Production ofPeptidesandProteins 75
K. Düring
Introduction 76
Advantages 76
Perspectives 80
Applications 81
Antibodies: avaluable example forproteinproduction in transgenicplants 81
Small peptides: a challenging type of proteins to be produced in transgenic plants 82
Application ofpeptides for plant resistance engineering 82
Summary 83
References 84
Chapter 7
Assembly Modulation of Channel-forming Peptides 87
S. Futaki
7.1. Introduction 87
7.2. Assemblycontroloftransmembranepeptidesthroughextramembranepeptide
segments 91
7.3. Conclusions 102
Acknowledgement 102
References 102
vii
Chapter 8
Molecular Casting of Infectious Amyloids, Inorganic and Organic Replication:
Nucleation, Conformational Change and Self-assembly 105
D.C. Gajdusek
8.1. Abstract 105
8.2. Introduction 105
8.3. Fantasy of a ‘‘Virus’’ without Carbon Atoms 106
8.4. Material Science andEngineering ofSelf-assembling Inorganic - Organic
ComplexSolids 107
8.5. AmyloidEnhancingFactorsare Scrapie-LikeAgents 107
References 110
Chapter 9
Structure and Stabilisation ofSelf-assembling Peptide Filaments 113
N.J. Gay, M. Symmons, M. Martin-FernandezandG.Jones
Abstract 113
9.1. Introduction 113
9.2. AsingleunitLRRfromtheTollreceptorformsspontaneouslyintofilaments 115
9.3. The conservedamide residue ofLRRN plays acriticalrole in filament
polymerisation 116
9.4. Predispositionstoamyloiddiseaseofteninvolvemutationtoamideresidues 118
9.5. Howcanwe studyearlyevents infilamentformation? 120
9.6. References 122
Chapter10
Designed Combinatorial Libraries of Novel Amyloid-like Proteins 127
M.H. Hecht, M.W.West,J.Patterson,J.D. Mancias,J.R. Beasley, B.M. Broome
andW.Wang
10.1. Abstract 127
10.2. Introduction 127
10.3. Results 128
10.4. Discussion 136
References 137
Chapter 11
DesignofSyntheticBranchedChainPolymericPolypeptidesforTargeting/Delivering
BioactiveMolecules 139
F. Hudecz
11.1. Introduction 139
11.2. Synthesis and Chemical Structure 142
11.3. Chemical Characterisation of Branched Polypeptides 147
11.4. Interaction of Polymers with Phospholipid Mono- and Bilayers 150
11.5. Biological Properties ofBranchedPolypeptides 151
11.6. Conjugates with Branched Polypeptides 155
11.7. Acknowledgement 156
11.8. References 156
viii
Chapter12
Amyloid-like Fibrils from a Peptide-analogueofthe Central Domain ofSilkmoth
ChorionProteins 161
V.A. Iconomidou and S.J. Hamodrakas
Results 163
Discussion 167
Acknowledgements 168
References 168
Chapter 13
Amyloidogenesis ofIsletAmyloid Polypeptide (IAPP) 171
A. Kapurniotu
Introduction 171
ResultsandDiscussion 172
Conclusions 184
Acknowledgements 184
References 184
Chapter 14
Engineering Self-assembly ofPeptides byAmphiphilic 2DMotifs:
α -to β TransitionsofPeptides 187
H.Mihara,Y.Takahashi,I.ObatayaandS.Sakamoto
14.1. Introduction 187
14.2. PeptidesThatUndergoAutocatalyticα→ β TransitionsandAmyloidFormation 188
14.3. Regulation of α/β -Folding of a Designed Peptide by a Heme Cofactor 198
14.4. ConclusionandFutureDirections 202
14.5. Acknowledgements 202
14.6. References 203
Chapter 15
Model Signal Peptides: Probes ofMolecularInteractions During Protein Secretion 207
A.Miller,L. WangandD.A.Kendall
Abstract 207
15.1. Introduction 207
15.2. ResultsandDiscussion 209
15.3. Conclusions 218
15.4. References 219
Chapter 16
Structure, Folding andAssembly ofAdenovirusFibers 221
A. Mitraki, M. van Raaij, R. Ruigrok, S. Cusack, J.-F. Hernandez and M. Luckey
Abstract 22 1
Morphology of the fiber 22 1
The fiber as a model system for folding and assembly 223
Thefiberunfoldsviaastableintermediatecomprisingtheheadandpartoftheshaft 225
Crystal structure of the stable domain 228
Assembly versus misassembly of the fibers 23 1
The adenovirus fiber as a model for synthetic fiber design 23 1
ix
Perspectives 232
Acknowledgements 233
References 233
Chapter17
Solving the Structure ofCollagen
A.Rich
Followthatfiber 235
Chasing Collagen 236
Structure ofcollagen 238
References 240
Chapter18
Disulfide Bond Based Self-assemblyofPeptides Leadingto Spheroidal Cyclic
Trimers 243
,
M.Royo,M.A. Contreras,J.Cebrián,E. Giralt,F.AlbericioandM.Pons
Abstract 243
18.1. Covalentpeptideself-assembly 243
18.2. Spontaneous cyclic trimerformationbybis-cysteinepeptides 246
18.3. Sequencevariability 248
18.4. Serine residues inthecentralpositions are essential fortrimerformation 251
18.5. Trimerformation arises fromfrustratedparalleldimers 252
18.6. Applicationsprospects 254
18.7. Acknowledgements 255
18.8. References 256
Chapter19
ANew Circular Helicoid-Type Sequential Oligopeptide CarrierforAssembling
MultipleAntigenic Peptides 257
M. Sakarellos-Daitsiotis, V.TsikarisandC. Sakarellos
Abstract 257
19.1. Introduction 258
19.2. Concept and design of the Sequential Oligopeptide Carriers (SOCs) 258
19.3. Selectedapplications ofSOC-I and SOC-II 259
n n
19.4. Synthetic aspectsofSOCs andconjugates 263
19.5. Conformational studyofSOCs andconjugates 264
19.6. Biologicalstudies 266
19.7. Conclusions 268
References 269
Chapter 20
Molecular Recognition in the Membrane: Role in the Folding of Membrane Proteins 273
Y. Shai
20.1. Introduction 273
References 288
x
Chapter 21
Novel PeptideNucleicAcidswith Improved Solubility andDNA-bindingAbility 295
M. SisidoandM. Kuwahara
21.1. Introduction 295
21.2. Peptides that Contain α -AminoAcids withNucleobases onthe Side Chain 295
21.3. Peptides that Contain δ-AminoAcidswithNucleobases onthe SideChain 300
21.4. Sequence-SpecificHybridizationbetweenTwoArtificialNucleicAcidAnalogs 306
21.5. Conclusions 308
21.6. References 309
Chapter 22
ChiralLipidTubules 311
M.S. Spector, R.R. Price and J.M. Schnur
References 320
Chapter 23
∆ -T -Mechanismin the Design of Self-assembling Structures 323
t
D.W.Urry,L.Hayes, C. Luan,D. C. Gowda,D.McPherson,J.XuandT.Parker
Abstract 323
23.1. Introduction 324
23.2. Materials andMethods 329
23.3. Results 333
23.4. Discussion 339
23.5. Acknowledgments 340
23.6. References 340
Chapter 24
Self-assembling Peptide Systems in Biology and Biomedical Engineering 343
S. Zhang and M. Altman
24.1. Abstract 343
24.2. Introduction 343
24.3. Type I Self-assembling peptides 344
24.4. Type II Self-assembling peptides 352
24.5. Type III Self-assembling peptides 355
Acknowledgement 358
References 358
Index 36 1
FOREWORD
One of the major drivers in biological research is the establishment of structures and
functions of the 50,000 or so proteins in our bodies. Each has a characteristic 3-
dimensional structure, highly "ordered" yet "disordered"! This structure is essential for
a protein's function and, significantly, it must be sustained in the competitive and
complex environment of the living cell.
It is now being recognised that when a cell loses control, proteins can self-
assemble into more complex supermolecular structures such as the amyloid fibres and
plaques associated with the pathogenesis of prion (CJD) or age-related (Alzheimer's)
diseases. This is a pointer to the wider significance of the self-assembling properties of
polypeptides. It has been long known that, in silk, polypeptides are assembled into ß-
sheet structures which impart on the material its highly exploitable properties of
flexibility combined with high tensile strength. But only now emerging is the
recognition that peptides can Self-assemble into a wide variety of non-protein-like
structures, including fibrils, fibres, tubules, sheets and monolayers. These are exciting
observations and, more so, the potential for materials and medical exploitations is so
wide ranging that over 80 scientists from Europe, USA, Japan and Israel. met 1-6 July
1999 in Crete, to discuss the wide-ranging implications of these novel developments.
Therewas a spiritof excitementaboutthe workshop indicative ofan important
new endeavor. The emerging perception is that of a new class of materials set to
become commercially viable early in the 21st century. This stems from the
opportunities for processing by the self-assembly route combined with the fact, just as
in the case of proteins, that functionality can be designed into the self-assembled
structures. They can be made responsive to pH change, mechanical forces, temperature,
pressure, electro-chemical potential, electrical and magnetic fields, and light. They can
function as sensors and actuators and can act as molecular motors capable of
interconverting energies ( vis-à-vis metabolism). They can even be programmed for
biodegradation! Extraordinary and widely exploitable properties. Particularly in view of
the exceptional thermal stability of peptides (up to 350°C). Nor are production costs
insurmountable. Large scale production by the fermentation or transgenic plant or
animal routes, at the ton level if needed, are already being developed. Projected costs
are as low as a few pounds per kilogram. Applications in tissue engineering, biomedical
devices, industrial fluids and personal care products are all under development. Could
thesenewmaterialsbecomethewonderpolymersof the21stcentury!
The workshop was charged with a vibrant atmosphere as may be expected of
this newly developing interdisciplinary area. As Francis Crick best put it "In Nature
hybrid species are usually sterile, but in science the reverse is often true. Hybrid
subjects are often astonishingly fertile, whereas if a scientific discipline remains too
pure it usually wilts".
In view of the exciting prospects for this new area of endeavor, it was felt that
it would be useful to record the proceedings of the workshop for those unable to attend.
xi
