A glycosynthase catalyst for the synthesis of flavonoid glycosides
A glycosynthase catalyst for the synthesis of flavonoid glycosides
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DOI：
10.1002/anie.200604177
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Davis, Benjamin G.
中科院分区：
文献类型：
--
作者：
Yang, Min;Davies, Gideon J.;Davis, Benjamin G.
亲脂性小分子的糖基化是在生物体中调节这些化合物的生物活性的主要策略之一。[1-4]事实上，即使是简单的植物，如拟南芥，也专门为这项任务提供了超过 120 个编码许多激活的糖依赖性糖基转移酶的开放阅读框。[5]此类化合物的新颖合成路线不仅提供了强大的工具，通过提供探针、标准品和抑制剂来探索这种活性，而且还提供了许多植物天然产物，例如黄酮类和类固醇糖苷，这些天然产物被认为是潜在的治疗方法。 [6-12] 尽管有许多优雅的化学糖基化方法，[13] 受体的直接区域选择性糖基化方法是有限的，[14] 这导致了对保护基团的严重依赖引入许多额外步骤的制度。生物催化方法通常具有精细的选择性，为克服此类问题提供了潜力。尽管使用糖基转移酶 (GT) 是糖苷键形成的天然解决方案，但获得合适的 GT 和供体限制了这种方法。 [15]此外，GT 的使用通常仅限于单个碳水化合物残基的转移。糖苷酶的使用为生物催化糖基化提供了一种替代方法。[16, 17] 糖苷酶促合成的最强大方法之一是 Withers 的“糖合酶”技术。[18–21] 糖合酶是基因工程改造的无亲核体突变型糖苷酶，可以催化形成糖苷。主要但不完全是通过使用糖基氟供体来实现糖苷键的连接，但不能水解产物。一个
Glycosylation of lipophilic small molecules is one of the predominant strategies by which the bioactivity of these compounds is modulated in living organisms.[1–4] Indeed, even simple plants, such as Arabidopsis thaliana, dedicate over 120 open reading frames encoding many activated sugar-dependent glycosyltransferases to this task alone.[5] Novel synthetic routes to such compounds provide a powerful tool for exploring not only this activity by providing ready access to probes, standards, and inhibitors but also to the many plant natural products such as flavonoids and steroid glycosides that have been implicated as potential therapeutics.[6–12] Despite the many elegant methods for chemical glycosylation,[13] methods for direct regioselective glycosylation of acceptors are limited,[14] which has led to a heavy dependence upon protecting-group regimes that introduce many additional steps. The often exquisite selectivity of biocatalytic methods provides the potential to overcome such problems. Although the use of glycosyltransferases (GTs) is nature s solution to glycoside bond formation, access to suitable GTs and donors limits this approach.[15] Furthermore, the use of GTs is typically limited to the transfer of only single carbohydrate residues.The use of glycosidases provides an alternative method for biocatalytic glycosylation.[16, 17] One of the most powerful approaches to the enzymatic synthesis of glycosides is Withers s “glycosynthase” technology.[18–21] Glycosynthases are genetically engineered nucleophile-less mutant glycosidases that can catalyze the formation of glycosidic linkages, primarily but not exclusively by using glycosyl fluoride donors, yet are incapable of hydrolysing the product. A