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RESEARCH PRODUCT
Dipeptidyl Nitroalkenes as Potent Reversible Inhibitors of Cysteine Proteases Rhodesain and Cruzain.
R. Luise Krauth-siegelNatalie DirdjajaBernd EngelsUte A. HellmichFlorenci V. GonzálezAntonio LatorrePatrick JoheJochen KesselringAnna HeilosSascha JungLledó Bou-iserteTanja SchirmeisterSantiago Rodríguezsubject
Chagas’ diseasechemistry.chemical_classificationChagas diseaseProteasescruzain010405 organic chemistryChemistrysleeping sicknessOrganic Chemistry010402 general chemistrymedicine.disease01 natural sciencesBiochemistry0104 chemical sciencesRhodesainEnzymeBiochemistryCovalent bondinhibitorsDrug DiscoverymedicineDialysis (biochemistry)Cysteinedescription
Dipeptidyl nitroalkenes are potent reversible inhibitors of cysteine proteases. Inhibitor 11 resulted to be the most potent one with Ki values of 0.49 and 0.44 nM against rhodesain and cruzain, respectively. According to enzymatic dilution and dialysis experiments, as well as computational and NMR studies, dipeptidyl nitroalkenes are tightly binding covalent reversible inhibitors. We thank Fundacion Española para la Ciencia y la Tecnología (Fecyt) and Generalitat Valenciana (AICO/2016/32) for financial support. T S. and B.E. thank the DFG (Deutsche Forschungsgemeinschaft) in the framework of the SFB630 for financial support. We thank Universitat Jaume I for technical suppport and funding. U.A.H. acknowledges support by the Carl-Zeiss foundation as well as the Center of Biomolecular Magnetic Resonance (BMRZ) funded by the state of Hesse.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-09-23 | ACS medicinal chemistry letters |