Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity
Michael F. Mesleh, Premraj Rajaratnam, Mary Conrad, Vasu Chandrasekaran, Christopher M. Liu, Bhaumik A. Pandya, You Seok Hwang, Peter T. Rye, Craig Muldoon, Bernd Becker, Johannes Zuegg, Wim Meutermans and Terence I. Moy
Article first published online: 9 OCT 2015 | DOI: 10.1111/cbdd.12662
Cell wall biogenesis for many clinically-relevant bacterial pathogens requires the activity of peptidoglycan glycosyltransferases. We report the synthesis of disaccharide-like compounds based on the peptidoglycan glycosyltransferase inhibitor moenomycin. We show, using a newly developed functional assay and NMR binding studies, that a subset of these compounds bind and inhibit peptidoglycan glycosyltransferase enzymes as expected.