Macrocyclic Antimicrobial Peptides Engineered from ω-Conotoxin.

ABSTRACT: The potent calcium channel blocker ω-conotoxin MVIIA is a linear cystine-knot peptide with multiple basic amino acids at both termini. This work shows that macrocyclization of MVIIA linking two positive-charge terminal clusters as a contiguous segment converts a conotoxin into an antimicrobial peptide. In addition, conversion of disulfide bonds to amino butyric acids improved the antimicrobial activity of the cyclic analogs. Ten macrocyclic analogs, with or without disulfide bonds, were prepared by both Boc and Fmoc chemistry using native chemical ligation. All cyclic analogs were active against selected Gram-positive and Gram-negative bacteria with minimal inhibitory concentrations in a low μM range. In contrast, MVIIA and its linear analog were inactive at concentrations up to 0.5 mM. Th

SUBMITTER: Hemu X 

PROVIDER: S-EPMC5470054 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature