Ehmke, VeronikaQuinsaat, Jose Enrico Q.Rivera-Fuentes, PabloHeindl, CorneliaFreymond, CelineRottmann, MatthiasBrun, RetoSchirmeister, TanjaDiederich, Francois2019-10-302019-10-302019-10-30201210.1039/c2ob00034bhttps://infoscience.epfl.ch/handle/20.500.14299/162492A series of aryl nitrile-based ligands were prepd. to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. D. functional theory calcns. provided relative reactivities of the nitriles, enabling prediction of their biol. affinity and cytotoxicity and a clear structure-activity relationship.Amino acidsarticleAryl nitrilearyl nitrile cysteine protease inhibitor sleeping sickness drug rhodesainBiological affinityCatalytic Domaincathepsin LCathepsin Lchemical structurechemistryCyanidesCysteine EndopeptidasesCysteine proteaseCysteine protease inhibitorscysteine proteinasecysteine proteinase inhibitorCysteine Proteinase InhibitorsDensity functional theoryDensity functional theory calculationsdrug antagonismdrug designDrug DesignElectrophilicityenzyme active siteenzymologyhumanHumansmetabolismModelsMolecularnitrileNitrilesRelative reactivitiesrhodesainStructure activity relationshipssynthesisTrypanosoma bruceiTrypanosoma brucei bruceitext::journal::journal article::research article