Variation in Ring Size of Cyclic Antimicrobial Peptides Results in Diversity and Selectivity of Biological Activity

Abstract

In continuing our efforts to understand the structure-function relationships in the cationic cyclic antimicrobial peptides [e.g.,1,2], the ring size was varied from 10 to 16 amino acids in a series of cyclic peptides based on the structure of GS 10 (a decameric analog of the antimicrobial peptide gramicidin S) to study the effect of changes in peptide size, structure, hydrophobicity and amphipathicity on biological activity. Similar to gramicidin S, GS 10 adopts a structure composed of an antiparallel β-sheet and two type II′ β-turns, is highly hemolytic and also quite active against a broad spectrum of bacteria and fungi [2]. The diversity in physicochemical and biological properties of the designed cyclic peptides of this study reveals the complex nature of their mechanism of biological activity.