STRUCTURE BASED DISCOVERY OF ANTIPARASITIC DRUGS AGAINST TRYPANASOMA CRUZI

$143,176P41FY2002RRNIH

Stanford University, Stanford CA

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Abstract

This proposal is to allow data collection from crystals with several different inhibitors bound to the T. cruzi HGPRTase. Lead compounds have been identified using bacterial complementation screening protocol developed by collaborators at U. of NC at Chapel Hill. Seven compounds have been identified as having higher inhibitory effect of the T. cruzi HPRTase than they have on the human HPRTase. Of these seven compounds identified to date, four of them have been tested in crystallizatioon experiments and have produced crystals of type #1. This ongoing effort to identify antiparasitic drugs will undoubtedly benefit from having the highest resolution data possible. Since some of the inhibitors only allow the growth of small crystals, synchrotron sources are indispensible to the long term goal of this project.

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