Development of a New Type of Protease Inhibitors, Efficacious against FIV and HIV Variants

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• 作者：Taekyu Lee ; Van-Duc Le ; Dongyeol Lim ; Ying-Chuan Lin ; Garrett M. Morris ; Andrew L. Wong ; Arthur J. Olson ; John H. Elder ; and Chi-Huey Wong
• 刊名：Journal of the American Chemical Society
• 出版年：1999
• 出版时间：February 17, 1999
• 年：1999
• 卷：121
• 期：6
• 页码：1145 - 1155
• 全文大小：499K
• 年卷期：v.121,no.6(February 17, 1999)
• ISSN：1520-5126

文摘

Based on the structural analysis of FIV protease and drug-resistant HIV proteases and molecularmodeling, a new type of inhibitors with a small P3 residue has been developed. These inhibitors are effectiveagainst HIV and its drug-resistant mutants, as well as SIV and FIV. Modification of existing HIV proteaseinhibitors by reducing the size of the P3 residue has the same effect. This finding provides a new strategy forthe development of HIV protease inhibitors effective against the wild-type and drug-resistant mutants. It furthersupports the use of FIV protease as a useful model for drug-resistant HIV proteases, which often have a moreconstricted binding region for the P3 group or the combined P3 and P1 groups.