covalent inhibitors of lgtc a blueprint for the discovery of non-substrate-like inhibitors for bacterial glycosyltransferases：（共价抑制剂lgtc蓝图的发现non-substrate-like细菌糖基转移酶的抑制剂）.pdfVIP

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covalent inhibitors of lgtc a blueprint for the discovery of non-substrate-like inhibitors for bacterial glycosyltransferases：（共价抑制剂lgtc蓝图的发现non-substrate-like细菌糖基转移酶的抑制剂）.pdf

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covalent inhibitors of lgtc a blueprint for the discovery of non-substrate-like inhibitors for bacterial glycosyltransferases：（共价抑制剂lgtc蓝图的发现non-substrate-like细菌糖基转移酶的抑制剂）

Bioorganic Medicinal Chemistry 25 (2017) 3182–3194 Contents lists available at ScienceDirect Bioorganic Medicinal Chemistry journal homepage: www.else /locate/bmc Covalent inhibitors of LgtC: A blueprint for the discovery of non-substrate-like inhibitors for bacterial glycosyltransferases Yong Xu a, Ruth Smith b, Mirella Vivoli c, Masaki Ema a, Niina Goos b, Sebastian Gehrke b,d, Nicholas J. Harmer c, Gerd K. Wagner a,⇑ a King’s College London, Department of Chemistry, Faculty of Natural Mathematical Sciences, Britannia House, 7 Trinity Street, London SE1 1DB, UK b King’s College London, Institute of Pharmaceutical Science, 150 Stamford Street, London SE1 9NH, UK c University of Exeter, Henry Wellcome Building for Biocatalysis, Stocker Road, Exeter EX4 4QD, UK d University of East Anglia, School of Pharmacy, Earlham Road, Norwich NR4 7TJ, UK a r t i c l e i n f o a b s t r a c t Article history: Non-substrate-like inhibitors of glycosyltransferases are sought after as chemical tools and potential lead Received 2 February 2017 compounds for medicinal chemistry, chemical biology and drug discovery. Here, we describe the discov- Revised 1 April 2017 ery of a novel small molecular inhibitor chemotype for LgtC, a retaining a-1,4-galactosyltransferase Accepted 4 April 2017 involved in bacterial lipooligosaccharide biosynthesis. The new inhibitors, which are structurally unre- Available online 11 April 2017 lated to both the donor and acceptor of LgtC, have low mic