Impact of Stereochemistry on Ligand Binding: X-ray Crystallographic Analysis of an Epoxide-Based HIV Protease Inhibitor
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- 作者：Fabio Benedetti ; Federico Berti ; Pietro Campaner ; Lidia Fanfoni ; Nicola Demitri ; Folasade M. Olajuyigbe ; Matteo De March ; Silvano Geremia
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2014
- 出版时间：September 11, 2014
- 年：2014
- 卷：5
- 期：9
- 页码：968-972
- 全文大小：339K
- ISSN：1948-5875
文摘
A new pseudopeptide epoxide inhibitor, designed for irreversible binding to HIV protease (HIV-PR), has been synthesized and characterized in solution and in the solid state. However, the crystal structure of the complex obtained by inhibitor鈥揺nzyme cocrystallization revealed that a minor isomer, with inverted configuration of the epoxide carbons, has been selected by HIV-PR during crystallization. The structural characterization of the well-ordered pseudopeptide, inserted in the catalytic channel with its epoxide group intact, provides deeper insights into inhibitor binding and HIV-PR stereoselectivity, which aids development of future epoxide-based HIV inhibitors.