title: Effect of the lipid II sugar moiety on bacterial transglycosylase: the 4-hydroxy epimer of lipid II is a TGase inhibitor.
abstract: Lipid II analogues bearing major modifications on the second sugar (GlcNAc) were synthesized and evaluated for their substrate activity toward TGases. Unexpectedly, N-deacetyled lipid II decreased its activity dramatically, and the C4-axial OH lipid II became an inhibitor (IC50= 8 μM) with an approximately 14-fold increase in binding affinity toward TGase (25 vs. 27).
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Guo
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Hu
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Hsiao-Han
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Ting-Jen R
authors.initials: TR
authors.lastname: Cheng
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei, 11529, Taiwan. wcheng@gate.sinica.edu.tw and Department of Chemistry, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan.
authors.forename: Wei-Chieh
authors.identifier: http://orcid.org/0000-0002-9319-3010
authors.initials: WC
authors.lastname: Cheng
mesh_terms: D016360:Clostridioides difficile / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D046928:Peptidoglycan Glycosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000073893:Sugars / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008055:Lipids; D000073893:Sugars; D046928:Peptidoglycan Glycosyltransferase