Naphthoquinones as covalent reversible inhibitors of cysteine proteases : studies on inhibition mechanism and kinetics
Molecules. Bd. 25. H. 9. Basel: MDPI 2020 Art. 2064
Erscheinungsjahr: 2020
ISBN/ISSN: 1420-3049
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
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Inhaltszusammenfassung
The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the...The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.» weiterlesen» einklappen
Autoren
Klassifikation
DDC Sachgruppe:
Biowissenschaften, Biologie
