NMR Detection and Study of Hydrolysis of HNO-Derived
Sulfinamides
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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)NH<sub>2</sub>] is unique to HNO. We have applied <sup>15</sup>N-edited <sup>1</sup>H 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