[NMR paper] NMR Detection and Study of the Hydrolysis of HNO-Derived Sulfinamides.

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NMR Detection and Study of the Hydrolysis of HNO-Derived Sulfinamides.

Related Articles NMR Detection and Study of the Hydrolysis of HNO-Derived Sulfinamides.

Biochemistry. 2013 Sep 27;

Authors: Keceli G, Moore CD, Labonte JW, Toscano JP

Abstract
Nitroxyl (HNO), a potential heart failure therapeutic, is known to post-translationally modify cysteine residues. Among reactive nitrogen oxide species, the modification of cysteine residues to sulfinamides [RS(O)NH2] is unique to HNO. We have applied 15N-edited 1H-NMR techniques to detect the HNO-induced thiol to sulfinamide modification in several small organic molecules, peptides, and the cysteine protease, papain. Relevant reactions of sulfinamides involve reduction to free thiols in the presence of excess thiol and hydrolysis to form sulfinic acids [RS(O)OH]. We have investigated sulfinamide hydrolysis at physiological pH and temperature. Studies with papain and a related model peptide containing the active site thiol suggest that sulfinamide hydrolysis can be enhanced in a protein environment. These findings are also supported by modeling studies. In addition, analysis of peptide sulfinamides at various pH values suggests that hydrolysis becomes more facile under acidic conditions.


PMID: 24073927 [PubMed - as supplied by publisher]



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