Conformationally Homogeneous Heterocyclic Pseudotetrapeptides as Three‐Dimensional Scaffolds for Rational Drug Design: Receptor‐Selective Somatostatin Analogues

• Published in: Angewandte Chemie International Edition 2009-01, Vol.48 (26), p.4725-4729
• Main Authors: Beierle, John M., Horne, W. Seth, van Maarseveen, Jan H., Waser, Beatrice, Reubi, Jean Claude, Ghadiri, M. Reza
• Format: Article
• Language: English
• Subjects: conformation analysis; Crystallography, X-Ray; cyclic peptides; Drug Design; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Humans; Molecular Conformation; Oligopeptides - chemistry; Protein Binding; Protein Isoforms - chemistry; Protein Isoforms - metabolism; Receptors, Somatostatin - chemistry; Receptors, Somatostatin - metabolism; Somatostatin - analogs & derivatives; Stereoisomerism; Structure-Activity Relationship; structure–activity relationships; triazoles
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.200805901

A would‐be amide: A 1,4‐disubstituted 1,2,3‐triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as β‐turn mimetics. High‐resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous β‐turn‐like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad‐spectrum activity. A would‐be amide: A 1,4‐disubstituted 1,2,3‐triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as β‐turn mimetics. High‐resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous β‐turn‐like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad‐spectrum activity.