Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries
Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries
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DOI：
10.1073/pnas.052703799
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发表时间：
2002-03-19
影响因子：
11.1
通讯作者：
Eliseev, AV
中科院分区：
文献类型：
--
作者：
Hochgürtel, M;Kroth, H;Eliseev, AV
神经氨酸酶是流感病毒繁殖的关键酶，已被用作从理论上高度多样化的动态组合文库中选择性地合成其自身抑制物的小亚集的模板。我们表明，库构建块，醛和胺，形成了相当数量的库组件，只有在酶存在的情况下，才能通过还原胺化作用将它们偶联。目标将最好的命中放大至少120倍。以这种体外虚拟模式合成和筛选的动态文库形成了具有高抑制活性的组分，独立合成的单个化合物的酶试验证实了这一点。
Neuraminidase, a key enzyme responsible for influenza virus propagation, has been used as a template for selective synthesis of small subsets of its own inhibitors from theoretically highly diverse dynamic combinatorial libraries. We show that the library building blocks, aldehydes and amines, form significant amounts of the library components resulting from their coupling by reductive amination only in the presence of the enzyme. The target amplifies the best hits at least 120-fold. The dynamic libraries synthesized and screened in such an in vitro virtual mode form the components that possess high inhibitory activity, as confirmed by enzyme assays with independently synthesized individual compounds.