Structure-based inhibitor design by using protein models for the development of antiparasitic agents.

作者：Christine S. Ring, Eugene Sun, James Hobson McKerrow, G K Lee, Philip Jon Rosenthal, Irwin D. Kuntz, Fred E. Cohen · 发表于：Proceedings of the National Academy of Sciences · 年份：1993 · DOI：10.1073/pnas.90.8.3583 · 被引用次数：268 · 研究领域：Computational Drug Discovery Methods、Malaria Research and Control、Biochemical and Molecular Research

The lack of an experimentally determined structure of a target protein frequently limits the application of structure-based drug design methods. In an effort to overcome this limitation, we have investigated the use of computer model-built structures for the identification of previously unknown inhibitors of enzymes from two major protease families, serine and cysteine proteases. We have successfully used our model-built structures to identify computationally and to confirm experimentally the activity of nonpeptidic inhibitors directed against important enzymes in the schistosome [2-(4-methoxybenzoyl)-1-naphthoic acid, Ki = 3 microM] and malaria (oxalic bis[(2-hydroxy-1-naphthylmethylene)hydrazide], IC50 = 6 microM) parasite life cycles.