Issue 19, 2018

How are 1,2,3-triazoles accommodated in helical secondary structures?

Abstract

1,4-Disubstituted-1,2,3-triazole (Tz) is widely used in peptides as a trans-amide bond mimic, despite having hazardous effects on the native peptide activity. The impact of amide bond substitution by Tz on peptide secondary structures is scarcely documented. We performed a Tz scan, by systematically replacing peptide bonds following the Aib residues with Tz on two model peptaibols: alamethicin F50/5 and bergofungin D, which adopt stable α- and 310 helices, respectively. We observed that the Tz insertion, whatever its position in the peptide sequences, abolished their antimicrobial activity. The structural consequences of this insertion were further investigated using CD, NMR and X-ray diffraction. Importantly, five crystal structures that were incorporated with Tz were solved, showing various degrees of alteration of the helical structures, from minor structural perturbation of the helix to partial disorder. Together, these results showed that Tz insertions impair helical secondary structures.

Graphical abstract: How are 1,2,3-triazoles accommodated in helical secondary structures?

Supplementary files

Article information

Article type
Paper
Submitted
20 Mar 2018
Accepted
12 Apr 2018
First published
12 Apr 2018

Org. Biomol. Chem., 2018,16, 3576-3583

How are 1,2,3-triazoles accommodated in helical secondary structures?

K. Ben Haj Salah, S. Das, N. Ruiz, V. Andreu, J. Martinez, E. Wenger, M. Amblard, C. Didierjean, B. Legrand and N. Inguimbert, Org. Biomol. Chem., 2018, 16, 3576 DOI: 10.1039/C8OB00686E

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