Antimicrobial and Chemotactic Activities of ω-Conotoxin Cyclic Analogues

Abstract

The family of ω-conotoxins isolated from paralytic venomous of Conus snails has been known to be an antagonist of presynaptic N-type calcium ion channels. They share certain similarities to the newly discovered family of antimicrobial macrocyclic peptides found in plant [1]. Both are basic peptides with a four-β-loop scaffold constrained by a cystine-knot disulfide motif. We have prepared three cyclic ω-conotoxin analogues with different disulfide constraints to determine whether the open-chain co-conotoxins are microbicidal and whether their activity can be improved by end-to-end cyclic analogues mimicking the plant macrocycles. In addition, we have also determined their hemolytic and chemotactic activities attendant to membranolytic and defense mechanisms of antimicrobials.