Cyclic peptide

About: Cyclic peptide is a research topic. Over the lifetime, 4338 publications have been published within this topic receiving 115310 citations. The topic is also known as: cyclic peptides & cyclic polypeptide.

Principles of peptide synthesis

Abstract: I. Introduction.- References.- II. Activation and Coupling.- 1 Activation.- 2 Coupling.- 3 Coupling Methods.- 3.1 The Azide Procedure.- 3.2 Anhydrides.- 3.3 Active Esters.- 3.4 Coupling Reagents.- 3.5 Auxiliary Nucleophiles.- 3.6 Enzyme-Catalyzed Formation of the Peptide Bond.- 3.7 Comment on Various Coupling Methods.- References.- III. Reversible Blocking of Amino and Carboxyl Groups.- 1 General Aspects.- 1.1 The Need for Protecting Groups.- 1.2 Minimal Versus Global Protection.- 1.3 Easily Removable Protecting Groups and Methods Used for Their Removal.- 1.3.1 Reduction and Oxidation.- 1.3.2 Acidolysis - Carbocation Formation.- 1.3.3 Proton Abstraction (Carbanion Formation).- 1.3.4 Nucleophilic Displacement.- 1.3.5 Photolysis.- 1.3.6 Enzyme Catalyzed Hydrolysis.- 2 Protection of the Carboxyl Group.- 2.1 Benzyl Esters and Substituted Benzyl Esters.- 2.2 Methyl Esters and Substituted Methyl Esters.- 2.3 Ethyl Esters and Substituted Ethyl Esters.- 2.4 tert-Butyl Esters and Related Compounds.- 2.5 Aryl Esters.- 2.6 Hydrazides.- 3 Protection of the Amino Group.- 3.1 Alkyl and Alkylidene Protecting Groups.- 3.2 Protection by Acylation.- 3.3 Protection of the Amino Group in the Form of Urethanes.- 3.3.1 Urethane Type Protecting Groups.- 3.3.2 Introduction of Urethane Type Protecting Groups.- 3.3.3 Removal of Urethane-Type Protecting Groups.- 3.4 Protecting Groups Derived from Sulfur and Phosphorus.- References.- IV. Semipermanent Protection of Side Chain Functions.- 1 Carboxyl Groups of Aspartyl and Glutamyl Residues.- 2 Side Chain Amino Groups of Lysine and Ornithine.- 3 Hydroxyl Groups in Serine, Threonine and Tyrosine.- 4 The Sulfhydryl Group in Cysteine.- 5 The Guanidino Group of Arginine.- 6 Imidazole in Histidine.- 7 The Thioether in Methionine.- 8 The Indole Nitrogen in Tryptophan.- 9 The Carboxamide Groups in Asparagine and Glutamine.- References.- V. Side Reactions in Peptide Synthesis.- 1 Side Reactions Initiated by Proton Abstraction.- 1.1 Racemization.- 1.1.1 Mechanisms of Racemization.- 1.1.2 Models for the Study of Racemization.- 1.1.3 Detection of Racemization (Examination of Synthetic Peptides for the Presence of Unwanted Diastereoisomers).- 1.1.4 Conservation of Chiral Purity.- 1.2 Undesired Cyclization.- 1.3 O-Acylation.- 2 Side Reactions Initiated by Protonation.- 2.1 Racemization.- 2.2 Undesired Cyclization.- 2.3 Alkylation.- 2.4 Chain Fragmentation.- 3 Side Reactions Due to Overactivation.- 4 Side Reactions Related to Individual Amino Acid Residues.- References.- VI. Tactics and Strategy in Peptide Synthesis.- 1 Tactics.- 1.1 Combinations of Protecting Groups.- 1.2 Final Deprotection.- 2 Strategies.- 2.1 Segment Condensation.- 2.2 Stepwise Synthesis Starting with the N-Terminal Residue (N?C Strategy).- 2.3 Stepwise Synthesis Starting with the C-Terminal Residue (C?W Strategy).- 3 Disulfide Bridges.- 4 Synthesis of Cyclic Peptides.- 4.1 Homodetic Cyclopeptides.- 4.2 Heterodetic Cyclopeptides.- 5 Sequential Polypeptides.- 6 Partial Synthesis (Semisynthesis).- References.- VII. Techniques for the Facilitation of Peptide Synthesis.- 1 Solid Phase Peptide Synthesis (SPPS).- 1.1 The Insoluble Support.- 1.2 The Bond Between Peptide and Polymer.- 1.3 Protection and Deprotection.- 1.4 Methods of Coupling in SPPS.- 1.5 Separation of the Completed Peptide Chain from the Polymeric Support.- 1.6 Problems in Solid Phase Peptide Synthesis.- 2 Synthesis in Solution.- 2.1 Peptides Attached to Soluble Polymers.- 2.2 The "Handle" Method.- 2.3 Synthesis "in situ".- 2.4 Synthesis Without Isolation of Intermediates.- References.- VIII Recent Developments, New Trends.- 1 Formation of the Peptide Bond.- 1.1 Acid Chlorides and Fluorides.- 1.2 Anhydrides.- 13 Active Esters.- 1.4 Coupling Reagents.- 1.5 Non-Conventional Formation of the Peptide Bond.- 1.6 Enzyme-Catalyzed Formation of the Peptide Bond.- 1.7 Cyclization and Formation of Disulfide Bridges.- 2 Protecting Groups.- 2.1 Blocking of the Carboxyl Function.- 2.2 Amine Protecting Groups.- 2.3 Masking of Functional Groups in the Side Chains of Amino Acids.- 2.4 Methods for the Introduction and Removal of Protecting Groups.- 3 Solid Phase Peptide Synthesis.- 4 Undesired Reactions in Peptide Synthesis.- 5 New Trends and Perspectives.- References.

N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists.

Abstract: The alpha(V)beta(3) integrin receptor plays an important role in human tumor metastasis and tumor-induced angiogenesis. The in vivo inhibition of this receptor by antibodies or by cyclic peptides containing the RGD sequence may in the future be used to selectively suppress these diseases. Here we investigate the influence of N-methylation of the active and selective alpha(V)beta(3) antagonist cyclo(RGDfV) (L1) on biological activity. Cyclo(RGDf-N(Me)V-) (P5) was found to be even more active than L1 and is one of the most active and selective compounds in inhibiting vitronectin binding to the alpha(V)beta(3) integrin. Its high-resolution, three-dimensional structure in water was determined by NMR techniques, distance geometry calculations, and molecular dynamics calculations, providing more insight into the structure-activity relationship.

Conformation and Biological Activity of Cyclic Peptides

Abstract: Cyclic peptides containing biologically active hormone sequences are suitable models for studying conformation-activity relationships. In such models the usual flexibility of peptide chains is reduced by their cyclic arrangement. However, conformational analysis of such systems by experimental means is possible only if a single conformer predominates at equilibrium, and criteria for this are put forward. NMR spectroscopic methods, including many recent advances, are discussed in relation to their ability to contribute to peptide conformational analysis.

Small Peptides as Potent Mimetics of the Protein Hormone Erythropoietin

Abstract: Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.