Jump to main content
Jump to site search

Issue 5, 2018
Previous Article Next Article

Conformational stabilization of a β-hairpin through a triazole–tryptophan interaction

Author affiliations

Abstract

Molecular tools to stabilize the β-hairpin conformation are needed as β-hairpin peptides are useful molecules for pharmaceutical, biological and materials applications. We explored the use of a “triazole bridge”, a covalent link between two β-hairpin strands obtained through Cu-catalyzed alkyne–azide cycloaddition, combined with an aromatic–aromatic interaction. Highly conformationally stable peptides were identified by NMR screening of a small collection of cyclic peptides based on the Trpzip2 scaffold. The characteristic Trp–Trp interaction of Trpzip2 was replaced by a diagonal triazole bridge of variable length. NMR and CD analyses showed that triazole and indole rings could favorably interact to stabilize a β-hairpin conformation. The conformational stabilization depends on the length of the triazole bridge and the reciprocal position between the aromatic rings. Combining aromatic interactions and the covalent inter-strand triazole bridge is a useful strategy to obtain peptides with a high β-hairpin content.

Graphical abstract: Conformational stabilization of a β-hairpin through a triazole–tryptophan interaction

Back to tab navigation

Supplementary files

Article information


Submitted
16 Nov 2017
Accepted
20 Dec 2017
First published
10 Jan 2018

Org. Biomol. Chem., 2018,16, 787-795
Article type
Paper

Conformational stabilization of a β-hairpin through a triazole–tryptophan interaction

D. Diana, C. Di Salvo, V. Celentano, L. De Rosa, A. Romanelli, R. Fattorusso and L. D. D'Andrea, Org. Biomol. Chem., 2018, 16, 787
DOI: 10.1039/C7OB02815F

Social activity

Search articles by author

Spotlight

Advertisements