Automated high-throughput synthesis of artificial glycopeptides. Small-molecule probes for chemical glycobiology
Automated high-throughput synthesis of artificial glycopeptides. Small-molecule probes for chemical glycobiology
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DOI：
10.1021/cc020001i
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发表时间：
2002-05-01
影响因子：
--
通讯作者：
Randell, KD
中科院分区：
文献类型：
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作者：
Arya, P;Barkley, A;Randell, KD
开发了一种全自动化的合成人工糖肽的方法，该人工糖肽在二肽支架上具有两个（相似或不同的）碳连接的糖基部分。通过使用这种结合肽/假肽和糖苷的多样性的方法，可以以高度受控的方式将不同的糖苷部分掺入肽/假肽主链上。该方法利用逐步还原胺化与糖苷醛衍生物（模型1）或（ii）糖苷还原胺化，然后糖苷酰胺键形成（模型2）。此外，自动化方法已被用于4 × 96人工糖肽的高通量文库合成。将这些文库作为酶系统的化学探针/抑制剂进行测试，所述酶系统在掺入鼠李糖单元之前将葡萄糖部分转化为鼠李糖，并且在分枝杆菌细胞壁的生物合成期间经由UDP-吡喃半乳糖苷酶将UDP-吡喃半乳糖转化为UDP-呋喃半乳糖。
A fully automated method Cor the synthesis of artificial glycopeptides having two (similar or different) carbon-linked glycosyl moieties on a dipeptide scaffold has been developed. By use of this approach that combines the diversity, of peptide/pseudopeptide and glycosides, different glycoside moieties can be incorporated onto the peptide/pseudopeptide backbone in a highly controlled manner. The approach utilizes a stepwise reductive amination with glycoside aldehyde derivatives (model 1) or (ii) glycoside reductive amination followed by glycoside amide bond formation (model 2). Further, an automated method has been utilized in the high-throughput library synthesis of 4 x 96 artificial glycopeptides. These libraries were tested as chemical probes/inhibitors of enzyme systems that convert a glucose moiety into rhamnose prior to incorporation of the rhamnose unit and the conversion of UDP-galactopyranose to UDP-galactofuranose via UDP-galactopyranose mutase enzyme during the biosynthesis of the mycobacterium cell wall.