Amino Acids, Peptides and Proteins in Organic Chemistry, Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis

by Hughes, Andrew B.

• ISBN13: 9783527321032
• ISBN10: 3527321039
• Edition: 1st
• Format: Hardcover
• Copyright: 2011-04-18
• Publisher: Wiley-VCH

Summary

Closing a gap in the literature, this is the only open book series to cover this important topic in organic and biochemistry. Drawing upon the combined expertise of the international "who's who" in amino acid research, this series is a real benchmark for amino acid chemistry, providing a comprehensive discussion of the occurrence, uses and applications of amino acids and, by extension, their polymeric forms, peptides and proteins. The practical value of each volume is heightened by the inclusion of experimental procedures.

Author Biography

Andrew Hughes is a reader and Head of the Department of Chemistry, La Trobe University, Melbourne, Australia. He obtained his degrees from the University of Western Australia. Post-doctoral appointments at the University of Cambridge starting 1989 included 3 years working with Professor Andrew Holmes before joining Professor Steven Ley's group in 1993. While at Cambridge he was appointed the Shell Research Fellow at Robinson College.

Table of Contents

Protection Reactions

General Considerations

Alpha-Amino Protection (Nalpha-Protection)

Carboxy Protection

Side Chain Protection

Photocleavable Protections

Conclusion

Experimental Section

The Huisgen Cycloaddition in Peptidomimetic Chemistry

Introduction

The Huisgen [2+3] Cycloaddition Between Azides and Acetylenes

Mechanistic Consideration for the Cu-Huisgen and Ru-Huisgen Cycloaddition

Building Blocks for the Synthesis of Triazole Modified Peptidomimetics

Cyclic Triazole Peptidomimetics

Acylic Triazole Peptidomimetics

Useful Experimental Procedures

Recent Advances in Beta-Strand Mimetics

Introduction

Macrocyclic Peptidomimetics

Acyclic Compounds

Aliphatic and Aromatic Carbocycles

Ligands Containing One Ring or Multiple Rings with One Heteroatom (O, S)

Ligands Containing One Ring with Two Heteroatoms (N,N)

Ligands Containing One Ring with Two Heteroatoms (N,S) or Three Heteroatoms (N,N,S or N,N,N)

Ligands Containing Two Rings with One Heteroatom (N or O)

Ligands Containing Two Rings with Two or Three Heteroatoms (N,N or N,S or N,N,N)

Concluding Remarks

Medicinal Chemistry of Alpha-Amino Acids

Introduction

Glutamic Acid

Conformational Restriction

Bioisosterism

Structure-Activity-Studies

Conclusion

Medicinal Chemistry of Alicyclic Beta-Amino Acids

Introduction

Five-Membered Alicyclic Beta-Amino Acids

Six-Membered Alicyclic Beta-Amino Acids

medicinal Chemistry of Alpha-Hydroxy-Beta-Amino Acids

Introduction

Alpha-Hydroxy-Beta-Amino Acids

Antibacterial Agents

Inhibitors of Aminopeptidases

Aspartyl Proteases Inhibitors

Paclitaxel and its Derivatives

Peptide Drugs

Lights and Shades of Peptide and Protein Drugs

Peptide Drugs Available on the Market

Approved Peptides in Oncology

Antimicrobial Peptides

Perspectives

Oral Bioavailability of Peptide and Peptidomimetic Drugs

Introduction

Fundamental Considerations of Intestinal Absorption

Barriers Limiting Oral Peptide/Peptidomimetic Drugs Bioavailability

Strategies to Improve Peptide-Based Drugs Oral Bioavailability

Conclusions

Asymmetric Synthesis of Beta-Lactams Via the Staudinger Reaction

Introduction

The Staudinger Reaction

Influence of the Geometry of the Imine on Stereoselectivity in the Reaction

Influence of the Polarity of the Solvent on Stereoselectivity of the Reaction

Influence of the Isomerization of the Imine Prior to its Nucleophilic Attack onto the Ketene Stereoselectivity in the Reaction

Influence of the Order of Addition of the Reactants to the Reaction

Influence of Chiral Substituents on the Stereoselectivity of the Reaction

Asymmetric Induction from the Imine Component

Asymmetric Induction from the Ketene Component

Double Asymmetric Cycloinduction

Influence of Catalysts on the Stereoselectivity of the Reaction

Concluding Remarks

Advances in N- and O-Glycopeptide Synthesis - A Tool to Study Clycosylation and Develop New Therapeutics

Introduction

O-Glycopeptide Synthesis

Synthesis of Mucin Type Glycopeptides

Synthesis of Tumor-Associated Glycopeptides and Glycopeptide Vaccines

Synthesis of Tn, T, sialyl Tn, sialyl T Glycosylated Amino Acid Building Blocks

Synthesis of Tn, T, sialyl Tn, sialyl T Glycopeptides and Vaccines

Synthesis of Glycopeptide Recognition Domain of P-Selectin Glycoprotein Ligand 1 (PSGL-1)

Synthesis of a Core 2 sLe AMino Acid Building Block Including a sLe Mimic

Synthesis of Unsulfated and Sulfated Core 2 sLe and Core 2 sLe Mimic PSGL-1 Glycopeptides

Chemoenzymatic Synthesis of Unsulphated and Sulphated Sialyl Lewis PSGL-1 Glycopeptide

Synthesis of Other Types of O-Glycopeptides

Synthesis of Fmoc-GlcNAc-Ser/Thr Amino Acids

Synthesis of Estrogene Receptor Peptides for Conformational Analysis

Synthesis of N-Glycopeptides

Synthesis of Ribonuclease C (RNase C) Glycoprotein

Synthesis of Erythropoietin N-Glycopeptide Fragment 1-28

Synthesis of Biantennary Dodecasaccharide

Synthesis of N-Glycopeptide Fragment 1-28

Chemoenzymatic Synthesis of a HIV GP120 V3 Domain N-Glycopeptide

Synthesis of the Oxazoline Tetrasaccharide Donor

Synthesis of Fmoc-GlcNAc-Asn Amino Acid Building Block

Synthesis of V3 Cyclic GlcNAc Peptide and Endo A Coupling with Man3GlcNAc Oxazoline Donor

Recent Developments in Neoglycopeptide Synthesis

Introduction

Neoglycoside and Neoglycopeptide Synthesis

Protein Side-Chain Modifications

Cu-Catalyzed Azide-Alkyne "Click" Cycloaddition

Cross Metathesis

Application of Neoglycopeptides as Synthetic Vaccines

Enzymatic, Molecular and Cell Biological Techniques

Combinatorial/Library Peptide Synthesis

Introduction

High Throughput Synthesis of Peptides

Peptide Libraries

Future of Peptide Libraries

Synthetic Protocols

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