New Cathepsin Inhibitors to Explore the Fluorophilic Properties of the S 2 Pocket of Cathepsin B: Design, Synthesis, and Biological Evaluation
| Autor: | Joaquín Timoneda, Michael Gütschow, F. Javier Cañada, Luis P. Calle, Vanessa Rodrigo, Jesús Jiménez-Barbero, Carlos del Pozo, María Sánchez-Roselló, Santos Fustero, Mihiret T. Sisay, Jürgen Bajorath, Maxim Frizler |
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| Rok vydání: | 2011 |
| Předmět: |
Hydrocarbons
Fluorinated Stereochemistry Stereoisomerism hydrolases stereoselectivity Catalysis Cathepsin B Nitriles inhibitors Combinatorial Chemistry Techniques Humans Molecule fluorinated ligands Biological evaluation Cathepsin Molecular Structure ligands Chemistry Organic Chemistry Dipeptides General Chemistry fluorinated fluorinated Design synthesis Drug Design peptides Stereoselectivity |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname CHEMISTRY-A EUROPEAN JOURNAL r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | 5 páginas, 1 figura, 2 tablas -- PAGS nros. 5256-5260 Fluor-in or out? Based on β,β-difluorinated cycloaliphatic amino acids, a library of new dipeptide nitriles was evaluated as human cathepsin inhibitors. The orientation of the fluorinated face relative to the protein structure of cathepsin B was elucidated by molecular modeling and NMR studies (see figure). For (R)-configured eutomers, the fluorine atoms are directed to the S2 pocket, whereas in (S)-configured distomers, the fluorinated face is solvent-exposed This work was supported by a grant from the Ministry of Science and Innovation of Spain (CTQ2007-61462/BQU, CTQ2006-10874-C02-01/BQU, CTQ2009-08536, CTQ2010-19774-C02, and GV/PROMETEO/2010/061). V.R. expresses their thanks for a predoctoral fellowship. C.d.P. and M.S.R thank the same institution for a Ramón y Cajal and a Juan de la Cierva contract, respectively. M.F. is supported by a fellowship from the NRW Forschungsschule Biotech-Pharma, and M.T.S. by a fellowship from the Graduiertenkolleg (GRK) 677 of the Deutsche Forschungsgemeinschaft |
| Databáze: | OpenAIRE |
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