Molecular Info®

Molecular Info® Copy Right © 2001 Institute of Molecular Development LLC

Antibacterial agents based on the cyclic D,L-a-peptide architecture SARA FERNANDEZ-LOPEZ, HUI-SUN KIM, ELLEN C. CHOI, MERCEDES DELGADO, JUAN R. GRANJA, ALISHER KHASANOV, KARIN KRAEHENBUEHL, GEORGINA LONG, DANA A. WEINBERGER, KEITH M. WILCOXEN & M. REZA GHADIRI The Nature, July 2001, 412, 452-455. Six- and eight-residue cyclic D,L-a-peptides act preferentially on Gram-positive and/or Gram-negative bacterial membranes compared to mammalian cells, increase membrane permeability, collapse transmembrane ion potentials, and cause rapid cell death. The effectiveness of this class of materials as selective antibacterial agents is highlighted by the high efficacy observed against lethal methicillin-resistant Staphylococcus aureus infections in mice. Cyclic D,L-a-peptides are proteolytically stable, easy to synthesize, and can be derived from a potentially vast membrane-active sequence space. The unique abiotic structure of the cyclic peptides and their quick bactericidal action may also contribute to limit temporal acquirement of drug resistant bacteria. The low molecular weight D,L-a-peptides offer considerable potential in combating a variety of existing and emerging infectious diseases.