Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity.

摘要: Synthesis of bacterial cell wall peptidoglycan requires glycosyltransferase enzymes that transfer the disaccharide-peptide from lipid II onto growing glycan chain. The polymerization chain precedes cross-linking by penicillin-binding proteins and is essential for growth key pathogens. As such, glycosyltransferases are an attractive target antibiotic drug discovery. However, significant challenges to development inhibitors these targets include suitable assays chemical matter suited nature binding site. We developed enzymatic activity using natural products moenomycin vancomycin as model inhibitors. In addition, we designed a library disaccharide compounds based on minimum fragment with inhibitory more drug-like synthetically versatile building block. A subset bound inhibited enzymes, could serve entry points development.