Tetrahydrobenzothiophene derivatives: conformationally restricted inhibitors of type II dehydroquinase
| Autor: | José M. Otero, Antonio L. Llamas-Saiz, L. Tizon, Alastair R. Hawkins, Mark J. van Raaij, Heather K. Lamb, Gavin C. Fox, Sonia Paz, Adrian J. Lapthorn, Concepción González-Bello, Luis Castedo |
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| Rok vydání: | 2010 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Models Molecular Magnetic Resonance Spectroscopy Stereochemistry Chemistry Protein Conformation Organic Chemistry Nuclear magnetic resonance spectroscopy Reaction intermediate Thiophenes Lyase Biochemistry Catalysis Anti-Bacterial Agents Enzyme Protein structure Drug Discovery Molecular Medicine General Pharmacology Toxicology and Pharmaceutics Tyrosine Enzyme Inhibitors Hydro-Lyases |
| Zdroj: | ChemMedChem. 6(2) |
| ISSN: | 1860-7187 |
| Popis: | Restriction is good for inhibition! Tetrahydrobenzothiophene-derived rigid mimics of the typeII dehydroquinase (DHQ2)-catalyzed reaction intermediate are reported. These derivatives fix the interaction with the tyrosine, the base that initiates the enzymatic reaction, in an inappropriate orientation for catalysis. Two competitive inhibitors in the series, 2-propenyl derivative 5e and 2-cyclopropylethyl compound 5i (shown), were crystallized in complex with DHQ2 from Helicobacter pylori, and the X-ray structures were determined at 1.95A and 1.85A, respectively. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Databáze: | OpenAIRE |
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