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

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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

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Publication details

The article was received on 16 Nov 2017, accepted on 20 Dec 2017 and first published on 10 Jan 2018


Article type: Paper
DOI: 10.1039/C7OB02815F
Citation: Org. Biomol. Chem., 2018, Advance Article
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    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, Advance Article , DOI: 10.1039/C7OB02815F

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