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Cyclized Helical Peptides: Synthesis, Properties and Therapeutic Applications [Kõva köide]

  • Formaat: Hardback, 240 pages, kõrgus x laius x paksus: 244x170x18 mm, kaal: 624 g
  • Ilmumisaeg: 21-Jul-2021
  • Kirjastus: Blackwell Verlag GmbH
  • ISBN-10: 3527343423
  • ISBN-13: 9783527343423
Teised raamatud teemal:
  • Formaat: Hardback, 240 pages, kõrgus x laius x paksus: 244x170x18 mm, kaal: 624 g
  • Ilmumisaeg: 21-Jul-2021
  • Kirjastus: Blackwell Verlag GmbH
  • ISBN-10: 3527343423
  • ISBN-13: 9783527343423
Teised raamatud teemal:

An important and timely guide to the progress being made on constrained helical peptides

Constraint helical peptides have emerged as a solution to target previously undruggable protein-protein interactions, which feature large and complex surfaces. Cyclized Helical Peptides: Synthesis, Properties and Therapeutic Applications offers a review of the most current methodologies of constructing constrained helices. The authors noted experts on the topic include the information on the fundamental features of cyclized helical peptides and discuss their limitations. The book summarizes and explores the effects of chemical methods constructing helical peptides on helicity, binding affinity, cell penetration, and nonspecific toxicity.

The book examines the therapeutic applications of the constraint helices and includes comparison with existing small molecule modulators or antibodies. Designed as a useful resource for both those outside and inside the field. Those new to the field will find a comprehensive introduction to cyclized helical peptide and those inside the field will find a deeper understanding of the topic.

This important book:

  • Offers a practical introduction to constrained helical peptides
  • Includes all aspects of constrained helical peptides
  • Includes information on the most recent methods that have emerged
  • Presents a guide to help solve practical problems in the field

Written for academics, pharmaceutical professional, Cyclized Helical Peptides is a comprehensive guide to the developments of constrained helical peptides.

1 Introduction
1(34)
1.1 Protein-Protein Interactions and Their Small-Molecule Modulators
1(7)
1.1.1 Characteristics of Protein-Protein Interactions
1(2)
1.1.2 Intervention of Protein-Protein Interactions Using Small Molecules
3(2)
1.1.2.1 Leukocyte Function-Associated Antigen-1
5(1)
1.1.2.2 Inhibitor of Apoptosis Proteins
6(1)
1.1.2.3 Bromodomains
6(1)
1.1.2.4 Human Immunodeficiency Virus Integrase
6(1)
1.1.2.5 B-Cell Lymphoma-2 Family/B-Cell Lymphoma-2 Homology 3 Proteins Interaction
7(1)
1.1.2.6 Mouse Double Minute 2-p53 Interaction
7(1)
1.2 Features of Peptide as Molecular Tools
8(4)
1.2.1 Advantages of Peptides as Molecular Tools
8(3)
1.2.2 Disadvantages of Peptides as Molecular Tools
11(1)
1.3 Helical Structures and Their Characterization
12(6)
1.3.1 Different Types of Helices
12(1)
1.3.1.1 a-Helix
12(1)
1.3.1.2 310-Helix
12(1)
1.3.1.3 Tt-Helix
13(2)
1.3.2 Characterization of Helical Peptides
15(1)
1.3.2.1 Circular Dichroism
15(1)
1.3.2.2 X-ray Crystallography
16(1)
1.3.2.3 Nuclear Magnetic Resonance (NMR)
17(1)
1.4 Stabilization of Peptides
18(9)
1.4.1 Peptide Stabilization via Cyclization
18(1)
1.4.1.1 Monocyclization
18(1)
1.4.1.2 Multicyclization
19(2)
1.4.2 Peptide Stabilization via Backbone Reconstruction
21(1)
1.4.2.1 Methylation
21(2)
1.4.2.2 Foldamers
23(4)
References
27(8)
2 Construction of Constrained Helices
35(34)
2.1 Side-Chain Cross-linking
35(22)
2.1.1 Disulfide Bond
35(2)
2.1.2 Amide and Ester
37(5)
2.1.3 All-Hydrocarbon Stapled Peptide
42(6)
2.1.4 Thioether
48(8)
2.1.5 Azole
56(1)
2.2 End Nucleation
57(5)
2.2.1 Macrocycle-Based N-cap Templates
58(2)
2.2.2 Hydrogen Bond Surrogate Approaches
60(1)
2.2.3 N-Terminal Side Chain Constrains as Helix-Nucleating Templates
61(1)
References
62(7)
3 Properties of Stabilized Peptides
69(38)
3.1 Helicity
69(11)
3.1.1 Ring Size
69(5)
3.1.2 Rigidity
74(5)
3.1.3 Comparison
79(1)
3.2 Binding Affinity
80(4)
3.2.1 Helicity
80(1)
3.2.2 Cyclization Position
81(3)
3.2.3 Substitution
84(1)
3.3 Cell Permeability
84(5)
3.3.1 Amphiphilicity: Hydrophobicity and Isoelectric Point
84(3)
3.3.2 Helicity
87(2)
3.3.3 Summary
89(1)
3.4 Nonspecific Toxicity
89(8)
3.5 Stability
97(1)
3.5.1 Proteolytic Stability
91(4)
3.5.2 Pharmacokinetic Properties
95(3)
3.6 Additional Features
98(5)
References
103(4)
4 Applications of Constrained Helices
107(52)
4.1 Cancer
107(36)
4.1.1 MDM2/X
107(3)
4.1.2 B-Cell Lymphoma 2 (MCL-l/BCL-2/BCL-XL)-BID/Noxa/BAX/BIM/PUMA
110(4)
4.1.3 NOTCH
114(4)
4.1.4 Insulin Receptor Substrate 1
118(2)
4.1.5 Ras
120(4)
4.1.6 Rab
124(2)
4.1.7 β-Catenin BCL-9/AXIN
126(4)
4.1.8 Epidermal Growth Factor Receptor
130(5)
4.1.9 Estrogen Receptor a
135(3)
4.1.10 Hypoxia-Inducible Factor
138(2)
4.1.11 Embryonic Ectoderm Development - Enhancer of Zeste Homolog 2
140(3)
4.2 Infectious Disease
143(7)
4.2.1 HIV
143(5)
4.2.2 Respiratory Syncytial Virus F (RSV)
148(2)
4.3 Metabolic Disease
150(2)
4.3.1 Glucokinase-Phospho-BAD
150(2)
References
152(7)
5 Stabilized Peptide Covalent Inhibitors
159(22)
5.1 Methodologies of Peptide Covalent Inhibitor
159(3)
5.1.1 Covalent Warhead
160(2)
5.1.2 Stapling Method
162(1)
5.2 Applications
162(15)
5.2.1 BCL-2 Family Proteins As Target
163(1)
5.2.2 MDM2 and MDM4 As Target
164(4)
5.2.3 Sulfonium Tethered Peptide
168(8)
5.2.4 Others
176(1)
References
177(4)
6 Stabilized Peptide PROTAC
181(10)
6.1 Proteolysis-Targeting Chimera (PROTAC)
181(1)
6.2 Design of Peptide PROTAC
181(3)
6.2.1 Exploitation of E3 Ubiquitin Ligase-Recruiting Ligand
182(1)
6.2.2 Design of Stabilized Peptide Ligand
183(1)
6.2.3 Impact of Linker
184(1)
6.3 Therapeutic Applications of Stabilized Peptide PROTAC
184(4)
6.3.1 Targeting ERa
185(3)
6.3.2 Targeting β-Catenin
188(1)
References
188(3)
7 Stabilized Peptide for Drug Delivery
191(22)
7.1 Cell-Penetraying Peptides (CPPs)
191(5)
7.1.1 Classification of CPPs
192(1)
7.1.2 Mechanism of Cell Penetration of CPPs
193(1)
7.1.3 Applications of CPPs
194(2)
7.2 Cell-Permeable Cyclic Peptides (Cyclic CPPs)
196(8)
7.2.1 Cyclic CPPs-Mediated Drug Delivery
198(4)
7.2.2 Cyclo-RGD
202(2)
7.3 Co-assembly Nanocarrier System
204(2)
7.4 Examples of Stabilized Peptide Drugs
206(2)
References
208(5)
8 Outlook
213(10)
8.1 The Development of Peptide-Stabilizing Methods
213(5)
8.2 Applications of Stabilized Helical Peptides
218(2)
References
220(3)
Index 223
Zigang Li is a professor in School of Chemical Biology and Biotechnology of Peking University, and the executive deputy director and senior researcher in the Shenzhen Bay Laboratory Pingshan Translational Medicine Center.

Hui Zhao is an investment manager of Shenzhen Angel FOF, with experience in industry research and investment, in the field of innovative drugs and medical devices.

Chuan Wan is a post-doctoral student under the supervision of Prof. Zigang Li.