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Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi by Douglas M Freymann; Mary Anne Wenck; Juan C Engel; Jun Feng; Pamela J Focia; Ann E Eakin; Sydney P Craig III is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi about?

## Background: Currently, only two drugs are recommended for treatment of infection with trypanosoma cruzi, the etiologic agent of chagas' disease. these compounds kill the trypomastigote forms of the parasite circulating in the bloodstream, but are relatively ineffective against the intracellular stage of the parasite life cycle. neither drug is approved by the fda for use in the us. the hypoxanthine phosphoribosyltransferase (hprt) from t. cruzi is a possible new target for antiparasite chemotherapy. the crystal structure of the hprt in a conformation approximating the transition state reveals a closed active site that provides a well-defined target for computational structure-based drug discovery. ## Results: A flexible ligand docking program incorporating a desolvation correction was used to screen the available chemicals directory for inhibitors targeted to the closed conformation of the trypanosomal hprt. of 22 potential inhibitors identified, acquired and tested, 16 yielded k(i)'s between 0.5 and 17 microm versus the substrate phosphoribosylpyrophosphate. surprisingly, three of eight compounds tested were effective in inhibiting the growth of parasites in infected mammalian

Who reads Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi?

Author

Douglas M Freymann; Mary Anne Wenck; Juan C Engel; Jun Feng; Pamela J Focia; Ann E Eakin; Sydney P Craig III

Publisher

Elsevier Science; Elsevier ; Cell Press; Elsevier BV (ISSN 1074-5521)

Published

2001

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)