Chemoenzymatic Synthesis of Uridine Diphosphate-GlcNAc and Uridine Diphosphate-GalNAc Analogs for the Preparation of Unnatural Glycosaminoglycans

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• 作者：Sayaka Masuko ; Smritilekha Bera ; Dixy E. Green ; Michel We茂wer ; Jian Liu ; Paul L. DeAngelis ; Robert J. Linhardt
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：February 3, 2012
• 年：2012
• 卷：77
• 期：3
• 页码：1449-1456
• 全文大小：416K
• 年卷期：v.77,no.3(February 3, 2012)
• ISSN：1520-6904

文摘

Eight N-acetylglucosamine-1-phosphate and N-acetylgalactosamine-1-phosphate analogs have been synthesized chemically and were tested for their recognition by the GlmU uridyltransferase enzyme. Among these, only substrates that have an amide linkage to the C-2 nitrogen were transferred by GlmU to afford their corresponding uridine diphosphate(UDP)-sugar nucleotides. Resin-immobilized GlmU showed comparable activity to nonimmobilized GlmU and provides a more facile final step in the synthesis of an unnatural UDP-donor. The synthesized unnatural UDP-donors were tested for their activity as substrates for glycosyltransferases in the preparation of unnatural glycosaminoglycans in vitro. A subset of these analogs was useful as donors, increasing the synthetic repertoire for these medically important polysaccharides.