Bioorganic & Medicinal Chemistry 26 (2018) 2973–2983 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry journal homepage: www.elsevier.com/locate/bmc Structure-activity relationships in a new class of non-substrate-like covalent inhibitors of the bacterial glycosyltransferase LgtC a b b b b a,⇑ Yong Xu , Jon Cuccui , Carmen Denman , Tripty Maharjan , Brendan W. Wren , Gerd K. Wagner King’s College London, Department of Chemistry, Faculty of Natural & Mathematical Sciences, Britannia House, 7 Trinity Street, London SE1 1DB, UK Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, UK article i nfo abstract Article history: Lipooligosaccharide (LOS) structures in the outer core of Gram-negative mucosal pathogens such as Received 23 January 2018 Neisseria meningitidis and Haemophilus inﬂuenzae contain characteristic glycoepitopes that contribute sig- Revised 3 March 2018 niﬁcantly to bacterial virulence. An important example is the digalactoside epitope generated by the Accepted 4 March 2018 retaining a-1,4-galactosyltransferase LgtC. These digalactosides camouﬂage the pathogen from the host Available online 6 March 2018 immune system and increase its serum resistance. Small molecular inhibitors of LgtC are therefore sought after as chemical tools to study bacterial virulence, and as potential candidates for anti-virulence drug Keywords: discovery. We
Bioorganic & Medicinal Chemistry – Elsevier
Published: Jul 15, 2018
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