A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry
A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry
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DOI：
10.1021/ja0302836
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发表时间：
2003-08-13
影响因子：
15
通讯作者：
Wong, CH
中科院分区：
文献类型：
--
作者：
Lee, LV;Mitchell, ML;Wong, CH
岩藻糖基转移酶和一般糖基转移酶的有效抑制剂由于围绕糖基转移反应家族的固有障碍而一直难以捉摸。岩藻糖基转移酶的弱底物亲和力和低催化能力的问题通过招募额外的结合特征（在这种情况下是疏水相互作用）来抵消，以产生高亲和力抑制剂，24，Ki = 62 nM。该分子是从85个化合物的GDP-三唑库中鉴定的，这些化合物是通过叠氮化物和乙炔反应物之间的Cu（I）催化的[2 + 3]环加成反应产生的，然后在没有产物分离的情况下进行原位筛选。
Potent inhibitors of fucosyltransferases, and glycosyltransferases in general, have been elusive due to the inherent barriers surrounding the family of glycosyltransfer reactions. The problems of weak substrate affinity and low catalytic proficiency of fucosyltransferase was offset by recruiting additional binding features, in this case hydrophobic interactions, to produce a high affinity inhibitor,24, withKi= 62 nM. The molecule was identified from a GDP-triazole library of 85 compounds, which was produced by the Cu(I)-catalyzed [2 + 3] cycloaddition reaction between azide and acetylene reactants, followed by in situ screening without product isolation.