Genetically selected cyclic-peptide inhibitors of AICAR transformylase homodimerization

被引：77

作者：

Tavassoli, A ^{[1
]}

Benkovic, SJ ^{[1
]}

机构：

[1] Penn State Univ, Dept Chem, University Pk, PA 16802 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2005年 / 44卷 / 18期

关键词：

bioorganic chemistry; enzymes; inhibitors; library biosynthesis; peptides;

D O I：

10.1002/anie.200500417

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Graph Presented) Finding the needle in a haystack need not be as troublesome as once thought. By coupling disruption of protein-protein (X-X) interactions to host-cell survival (see figure), inhibitors of ATIC (a key enzyme in the de novo purine biosynthetic pathway) were readily identified from a biosynthesized library of 107 small molecules. The activity and selectivity of nine cyclic peptides selected by this method were demonstrated in vivo and in vitro. AICAR=aminoimidazole-4-carboxamide ribonucleotide. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：2760 / 2763

页数：4

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