Misbehaving Proteins (eBook)

Protein (Mis)Folding, Aggregation, and Stability

Regina Murphy, Amos Tsai (Herausgeber)

eBook Download: PDF
2007 | 2006
VIII, 354 Seiten
Springer New York (Verlag)
978-0-387-36063-8 (ISBN)

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This text provides an up-to-date collection of theoretical and experimental studies into protein folding, misfolding, aggregation, and stability. Additionally, issues faced during the development of protein products are illustrated. It contains an introductory chapter for readers new to the protein folding field. The book provides a thorough and clear discussion of computational approaches to understanding and modeling protein aggregation.


Misfoldedaggregatedproteinoncewasconsideredasinterestingasyesterday'strash-a bothersome by-product of important and productive activities, to be disposed of and forgotten as quickly as possible. Yesterday's trash has become today's focus of cons- erable scienti?c interest for at least two reasons: (1) protein aggregates are at the core of a number of chronic degenerative diseases such as Alzheimer's disease, and (2) - gregation poses signi?cant obstacles to the manufacture of safe, ef?cacious, and stable protein products. As interest in protein misfolding, aggregation, and stability has soared beyond the core group of traditional protein-folding scientists, and as substantial scienti?c progress in understanding and controlling protein misfolding has been achieved, the need to summarize the state of the art became manifest. Although there are many excellent texts and edited collections on protein structure and folding, these volumes tend to relegate protein misfolding and aggregation to a minor role. Review articles and books focused on the biological role of protein aggregates in diseases have been published recently. Misbehaving Proteins: Protein (Mis)folding, Aggregation, and Stability differs from theseotherrecenteffortsinitsemphasisonfundamentalcomputationalandexperimental studies and in its linkage of disparate consequences of protein misfolding (e.g., from clinical manifestations to manufacturing headaches) to their common causes.

Preface 5
Contents 7
Introduction 9
Protein Folding, Misfolding, Stability, and Aggregation 10
Mathematical Models and Computational Methods 21
Nonnative Protein Aggregation 22
Simulations of Protein Aggregation 52
Experimental Methods 83
Elucidating Structure, Stability, and Conformational Distributions during Protein Aggregation with Hydrogen Exchange and Mass Spectrometry 84
Application of Spectroscopic and Calorimetric Techniques in Protein Formulation Development 102
Small-Angle Neutron Scattering as a Probe for Protein Aggregation at Many Length Scales 127
Laser Light Scattering as an Indispensable Tool for Probing Protein Aggregation 149
X-ray Diffraction for Characterizing Structure in Protein Aggregates 168
Glass Dynamics and the Preservation of Proteins 193
Fundamental Studies in Model Systems 215
Folding and Misfolding as a Function of Polypeptide Chain Elongation 216
Determinants of Protein Folding and Aggregation in P22 Tailspike Protein 245
Factors Affecting the Fibrillation of a- Synuclein, a Natively Unfolded Protein 263
Molten Globule-Lipid Bilayer Interactions and Their Implications for Protein Transport and Aggregation 284
Protein Product Development 307
Self-Association of Therapeutic Proteins 308
Mutational Approach to Improve Physical Stability of Protein Therapeutics Susceptible to Aggregation 326
Index 346

Erscheint lt. Verlag 12.10.2007
Zusatzinfo VIII, 354 p. 137 illus., 17 illus. in color.
Verlagsort New York
Sprache englisch
Themenwelt Studium 1. Studienabschnitt (Vorklinik) Biochemie / Molekularbiologie
Naturwissenschaften Biologie Biochemie
Naturwissenschaften Biologie Mikrobiologie / Immunologie
Naturwissenschaften Chemie
Technik
Schlagworte biochemical engineering • Mutation • Polypeptide • Protein • Protein Folding • proteins • Protein sequence • Proteomics • Transport
ISBN-10 0-387-36063-8 / 0387360638
ISBN-13 978-0-387-36063-8 / 9780387360638
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