Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic Antimicrobial Chemotherapy.
Fiche publication
Date publication
janvier 2018
Journal
ACS medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VANDERESSE Régis
Tous les auteurs :
Le Guern F, Ouk TS, Ouk C, Vanderesse R, Champavier Y, Pinault E, Sol V
Lien Pubmed
Résumé
In order to highlight the potential of photodynamic antimicrobial chemotherapy in case of infections by antibiotic resistant-strains, a new antimicrobial peptide conjugate has been synthesized, consisting of a derivative of polymyxin B and a cationic porphyrin covalently attached together to a spacer. A polymyxin-derived moiety was subjected to a primary structural modification in the replacement of four diaminobutyrate residues with lysine ones. This modification was done in order to strongly reduce bactericidal activity, with the aim to eliminate the potential rise of polymyxin-resistant strains. Despite this modification, this new conjugate displayed a strong photobactericidal activity against Gram-positive as well as Gram-negative bacteria. It was further shown that this conjugate was able to strongly stick to the cell walls of either kind of strain, thus helping to inactivate bacteria through the production of reactive oxygen species under light irradiation.
Référence
ACS Med Chem Lett. 2018 Jan 11;9(1):11-16