Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan 31;16(5):787-795.
doi: 10.1039/c7ob02815f.

Conformational Stabilization of a β-Hairpin Through a Triazole-Tryptophan Interaction

Affiliations
Free article

Conformational Stabilization of a β-Hairpin Through a Triazole-Tryptophan Interaction

Donatella Diana et al. Org Biomol Chem. .
Free article

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.

Similar articles

See all similar articles
Feedback