title: Synthesis of 1-C-Glycoside-Linked Lipid II Analogues Toward Bacterial Transglycosylase Inhibition.
abstract: Preparation of Lipid II analogues containing an enzymatically uncleavable 1-C-glycoside linkage between the disaccharide moiety and the pyrophosphate- or pyrophosphonate-lipid moiety is described. The synthesis of a common 1-C-vinyl disaccharide intermediate has been developed that allows easy preparation of both an elongated sugar-phosphate bond and a sugar-phosphonate moiety, which are coupled with the polyprenyl phosphate to give the desired molecules. Inhibition studies show how a subtle structural modification results in dramatically different potency toward bacterial transglycosylase (TGase), and the results identify Lipid II-C-O-PP (IC50 =25 μM) as a potential TGase inhibitor.
authors.affiliation: The Genomics Research Center, Academia Sinica, No. 128, Academia Road, Sec. 2, Nankang District, Taipei, 11529 (Taiwan), Fax: (+886) 2-27899931.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Lin
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Chen
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Hu
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Yun
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Cheng
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry*; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006027:Glycosides; D016695:Glycosyltransferases / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: C438934:C-glycoside; D004791:Enzyme Inhibitors; D004798:Enzymes; D006017:Glycolipids; D006027:Glycosides; D008055:Lipids; D009005:Monosaccharides; D016695:Glycosyltransferases
keywords: antibiotics; cell cycle; glycolipids; glycosides; inhibitors