title: Reactivity of C-terminal cysteines with HNO.
abstract: Nitroxyl (HNO), a potential heart failure therapeutic, is known to target cysteine residues to form sulfinamides and/or disulfides. Because HNO-derived modifications may depend on their local environment, we have investigated the reactivity of HNO with cysteine derivatives and C-terminal cysteine-containing peptides at physiological pH and temperature. Our findings indicate that the nature of HNO-derived modifications of C-terminal cysteines is affected by the C-terminal carboxylate. Apart from the lack of sulfinamide formation, these studies have revealed the presence of new products, a sulfohydroxamic acid derivative (RS(O)2NHOH) and a thiosulfonate (RS(O)2SR), presumably produced under our experimental conditions via the intermediacy of a cyclic structure that is hydrolyzed to give a sulfenic acid (RSOH). Moreover, these modifications are formed independent of oxygen.
authors.affiliation: Department of Chemistry, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Gizem
authors.initials: G
authors.lastname: Keceli
authors.forename: John P
authors.initials: JP
authors.lastname: Toscano
mesh_terms: D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism*; D006868:Hydrolysis; D007097:Imines / Q000737:chemistry / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013434:Sulfenic Acids / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013452:Sulfonium Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: D007097:Imines; D009589:Nitrogen Oxides; D013434:Sulfenic Acids; D013438:Sulfhydryl Compounds; D013452:Sulfonium Compounds; C522016:sulfinimine; C039900:nitroxyl; D003545:Cysteine