Enzyme Isoselective Inhibitors: A Tool for Binding-Trend Analysis
| Autor: | Michael Shokhen, Rachel Ozeri, Nurit Perlman, Amnon Albeck, Netaly Khazanov |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Virtual screening Binding Sites Magnetic Resonance Spectroscopy Chemistry Stereochemistry Organic Chemistry Expert analysis Biochemistry Combinatorial chemistry Mass Spectrometry Catalysis Enzyme Covalent bond Drug Discovery Thermodynamics Molecular Medicine Enzyme Inhibitors General Pharmacology Toxicology and Pharmaceutics |
| Zdroj: | ChemMedChem. 1:631-638 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.200600029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text