title: Tuning and predicting biological affinity: aryl nitriles as cysteine protease inhibitors.
abstract: A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Hönggerberg, HCI, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Ehmke
authors.forename: Jose Enrico Q
authors.initials: JE
authors.lastname: Quinsaat
authors.forename: Pablo
authors.initials: P
authors.lastname: Rivera-Fuentes
authors.forename: Cornelia
authors.initials: C
authors.lastname: Heindl
authors.forename: Céline
authors.initials: C
authors.lastname: Freymond
authors.forename: Matthias
authors.initials: M
authors.lastname: Rottmann
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.forename: François
authors.initials: F
authors.lastname: Diederich
mesh_terms: D020134:Catalytic Domain; D056668:Cathepsin L / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000201:enzymology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D003546:Cysteine Endopeptidases; C446033:rhodesain; D056668:Cathepsin L