NMR Detection and Study of Hydrolysis of HNO-Derived Sulfinamides

详细信息    查看全文

• 作者：Gizem Keceli ; Cathy D. Moore ; Jason W. Labonte ; John P. Toscano
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：October 22, 2013
• 年：2013
• 卷：52
• 期：42
• 页码：7387-7396
• 全文大小：430K
• 年卷期：v.52,no.42(October 22, 2013)
• ISSN：1520-4995

文摘

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 p>15p>N-edited p>1p>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.