APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS

被引：157

作者：

EALICK, SE

BABU, YS

BUGG, CE

ERION, MD

GUIDA, WC

MONTGOMERY, JA

SECRIST, JA

机构：

[1] BIOCRYST INC,BIRMINGHAM,AL 35205

[2] CIBA GEIGY CORP,SUMMIT,NJ 07901

[3] SO RES INST,BIRMINGHAM,AL 35255

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 24期

关键词：

D O I：

10.1073/pnas.88.24.11540

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：

Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported.

引用

页码：11540 / 11544

页数：5

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