title: Ruthenium tris(2-pyridylmethyl)amine as an effective photocaging group for nitriles.
abstract: Ruthenium(II) tris(2-pyridylmethyl)amine (TPA) is an effective caging group for nitriles that provides high levels of control over the enzyme activity with light. Two caged nitriles were prepared, [Ru(TPA)(MeCN)2](PF6)2 (1) and [Ru(TPA)(3)2](PF6)2 (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH2CN, and characterized by various spectroscopic techniques and mass spectrometry. Both 1 and 2 show the release of a single nitrile within 20 min of irradiation with 365 nm light. Complex 2 acts as a potent, photoactivated inhibitor of human cathepsin K. IC50 values were determined for 2 and 3. Enzyme inhibition for 2 was enhanced by a factor of 89 upon exposure to light, with IC50 values of 63 nM (light) and 5.6 μM (dark).
authors.affiliation: Department of Chemistry, Wayne State University , 5101 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Rajgopal
authors.initials: R
authors.lastname: Sharma
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Knoll
authors.forename: Philip D
authors.initials: PD
authors.lastname: Martin
authors.forename: Izabela
authors.initials: I
authors.lastname: Podgorski
authors.forename: Claudia
authors.initials: C
authors.lastname: Turro
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Kodanko
mesh_terms: D056657:Cathepsin K / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008027:Light; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009570:Nitriles; D011725:Pyridines; D017975:Ruthenium Compounds; C431843:tris(2-pyridylmethyl)amine; D056657:Cathepsin K