Design, Synthesis and Analysis of a Cysteine-Deleted Analog of the Antimicrobial Peptide Tachyplesin-I

摘要

Tachyplesin I (KWCFRVCYRGICYRRCR-NH2) is a cyclic broad-spectrum antimicrobial peptide forming a rigid, antiparallel beta-sheet structure because of two intramolecular disulfide linkages. It is believed to act through a detergent-like mechanism due to amphipathic properties, permeabilizing bacterial membranes. The positive charge of the arginine and lysine residues confer specificity for bacterial membranes, as they are attracted to negatively charged phosphatidyl esters (mammalian membranes contain more positively charged or zwitterionic phospholipids). The hydrophobic part allows for penetration of the lipid membrane, disrupting membrane structure by creating holes and leading to cell death. Bacteria should not develop resistance to drugs that work through this mechanism.