naphthoquinones and phenylalanylleucine

naphthoquinones has been researched along with phenylalanylleucine* in 1 studies

Other Studies

1 other study(ies) available for naphthoquinones and phenylalanylleucine

Article	Year
Naphthoquinones as Covalent Reversible Inhibitors of Cysteine Proteases-Studies on Inhibition Mechanism and Kinetics. Molecules (Basel, Switzerland), 2020, Apr-28, Volume: 25, Issue:9 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. Topics: Cathepsin L; Cysteine Endopeptidases; Cysteine Proteases; Cysteine Proteinase Inhibitors; Dipeptides; Electrons; Esters; Hydrolysis; Inhibitory Concentration 50; Kinetics; Mass Spectrometry; Naphthoquinones; Prodrugs; Quantum Theory; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma brucei brucei	2020

Article

Year

Naphthoquinones as Covalent Reversible Inhibitors of Cysteine Proteases-Studies on Inhibition Mechanism and Kinetics.

Molecules (Basel, Switzerland), 2020, Apr-28, Volume: 25, Issue:9

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.

Topics: Cathepsin L; Cysteine Endopeptidases; Cysteine Proteases; Cysteine Proteinase Inhibitors; Dipeptides; Electrons; Esters; Hydrolysis; Inhibitory Concentration 50; Kinetics; Mass Spectrometry; Naphthoquinones; Prodrugs; Quantum Theory; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma brucei brucei

2020