Synthesis of 1‐C‐Glycoside‐Linked Lipid II Analogues Toward Bacterial Transglycosylase Inhibition |
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Authors: | Dr Cheng‐Kun Lin Kuo‐Ting Chen Chia‐Ming Hu Wen‐Yi Yun Prof Dr Wei‐Chieh Cheng |
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Affiliation: | The Genomics Research Center, Academia Sinica, No. 128, Academia Road, Sec. 2, Nankang District, Taipei, 11529 (Taiwan), Fax: (+886)?2‐27899931 |
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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. |
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Keywords: | antibiotics cell cycle glycolipids glycosides inhibitors |
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