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Stabilized Helical Peptide Therapeutics

Stabilized Helical Peptide Therapeutics

Zigang Li, Hui Zhao

ISBN: 978-3-527-34345-4

May 2019

850 pages

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$110.99

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Description

This book covers current methodologies of constructing constrained helices, including their features and limitations. The effects of chemical methods constructing helical peptides on helicity, binding affinity, cell penetration and nonspecific toxicity are also substantially summarized and discussed. Furthermore, therapeutic applications of the constraint helices, including comparison with existing small molecule modulators or antibodies are also included. This book will give readers outside the field a comprehensive introduction and readers inside the field a deeper understanding, thus it will help researchers to further advance the field or choose proper achievement of the field to solve practical problems.
PART I OVERVIEWS
1.1 Protein-protein interactions
1.1.1 Function
1.1.2 Structural basis and features
1.1.3 Targeting PPIs by small molecules
1.2 Peptides as molecular tools
1.2.1 Advantages
1.2.2 Disadvantages
1.3 Helical structures
1.3.1 Classification
1.3.2 Function
1.3.3 Characterization
1.4 Stabilization of helices via cyclization
1.4.1 Classification
1.4.2 Overview

PART II CONSTRUCTION OF CONSTRAINED HELICES
2.1 Side-chain crosslinking
(History, chemistry, features and limitations)
2.1.1 Disulfide bond
I+3, i+7, conotoxin
2.1.2 Amide or ester
2.1.3 All-hydrocarbon
I+4/3/7, stitched peptide, de alpha methylation, reduced, Moore
2.1.4 Thiol ether
I+3, Woolley, Heinis, Lin, DeGrado, Pentelute, Smith, Chou, Dawson, Li
2.1.5 Azole
Chorev, Spring, Arora
2.2 End nucleation
2.2.1 Hydrazone
2.2.2 All-hydrocarbon
Arora, Alewood
2.2.3 Disulfide bond
2.2.4 Thiol ether
2.2.5 Amide

PART III EFFECTS OF CYCLIZATION ON HELICES
3.1 Helicity
3.1.1 Ring size
3.1.2 Rigidity (alpha methylation, double bond, Z/E)
3.1.3 Substitution (chirality, group size)
3.1.4 Comparison
3.2 Binding affinity
3.2.1 Helicity
3.2.2 Cyclization position
3.2.3 Substitution
3.3 Cell permeability
3.3.1 Helicity
3.3.2 Hydrophobicity
3.3.3 Isoelectric point
3.4 Nonspecific toxicity
3.3.1 Helicity
3.3.2 Hydrophobicity
3.3.3 Isoelectric point

PART IV APPLICATIONS OF CONSTRAINED HELICES
(physiology and pathology of the target, small molecules/antibodies, structural basis, peptide modulators)
4.1 Cancer
ER, BCL-2, MDM2/X, HIF, NOTCH, RAS, beta-catenin, IRS1, Rab, EGFR, KRAS
4.2 Infectious Disease
HIV, bacteria, RSV
4.3 Nervous system disease
NMDA, Galanin, Neuropeptide Y
4.4 Respiratory system disease
Interleukin 13

PART V OUTLOOK
5.1 Methodology development
5.2 Applications