Enzyme isoselective inhibitors: a tool for binding-trend analysis |
| |
Authors: | Ozeri Rachel Khazanov Netaly Perlman Nurit Shokhen Michael Albeck Amnon |
| |
Affiliation: | The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan 52900, Israel. |
| |
Abstract: | A transition-state analogue inhibitor that covalently reversibly binds to an enzyme formally consists of two parts: the chemical site, CS and the recognition site, RS. We have experimentally and theoretically demonstrated that the trend of binding affinity in a series of isoselective inhibitors (with identical RS and different CS fragments) depends mainly on their CS fragments. Isoselective inhibitors have the same affinity trend toward different enzymes of the same family with a common catalytic mechanism. Thus, very good correlation between experimentally determined and theoretically calculated Ki values was demonstrated. A practical outcome is the application of the described method as a tool for an expert analysis in virtual screening of inhibitor libraries and in the design of new enzyme inhibitors. |
| |
Keywords: | binding trends drug design quantum chemistry serine proteases transition‐state analogues |
本文献已被 PubMed 等数据库收录! |
|