Le Guern Florent, Ouk Tan-Sothea, Ouk Catherine, Vanderesse Regis, Champavier Yves, Pinault Emilie, Sol Vincent
Université de Limoges, Laboratoire de Chimie des Substances Naturelles (LCSN), EA 1069, 123 Avenue Albert Thomas, 87060 Limoges Cedex, France.
Université de Limoges, BISCEm, 87000 Limoges, France.
ACS Med Chem Lett. 2017 Oct 17;9(1):11-16. doi: 10.1021/acsmedchemlett.7b00360. eCollection 2018 Jan 11.
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.
为了突出光动力抗菌化疗在抗生素耐药菌株感染情况下的潜力，合成了一种新的抗菌肽偶联物，它由多粘菌素B的衍生物和通过间隔基共价连接在一起的阳离子卟啉组成。对多粘菌素衍生部分进行了一级结构修饰，用赖氨酸取代了四个二氨基丁酸残基。进行这种修饰是为了大幅降低杀菌活性，以消除多粘菌素耐药菌株潜在的产生。尽管有这种修饰，这种新的偶联物对革兰氏阳性菌和革兰氏阴性菌都表现出很强的光杀菌活性。进一步表明，这种偶联物能够牢固地粘附在这两种菌株的细胞壁上，从而有助于在光照下通过产生活性氧使细菌失活。
