Target-induced formation of neuraminidase inhibitors from in vitro virtual combinatorial libraries

被引：115

作者：

Hochgürtel, M ^{[1
]}

Kroth, H ^{[1
]}

Piecha, D ^{[1
]}

Hofmann, MW ^{[1
]}

Nicolau, C ^{[1
]}

Krause, S ^{[1
]}

Schaaf, O ^{[1
]}

Sonnenmoser, G ^{[1
]}

Eliseev, AV ^{[1
]}

机构：

[1] Therascope AG, D-69120 Heidelberg, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 06期

关键词：

D O I：

10.1073/pnas.052703799

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：3382 / 3387

页数：6

共 28 条

[1] THE NEURAMINIDASE OF INFLUENZA-VIRUS [J].