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标题：Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries
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作者：Matthias Hochgürtel ; Heiko Kroth ; Dorothea Piecha 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：6
页码：3382-3387
DOI：10.1073/pnas.052703799
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.