Department of Chemistry, Johns Hopkins University , Baltimore, Maryland 21218, United States.
Biochemistry. 2014 Jun 10;53(22):3689-98. doi: 10.1021/bi500360x. Epub 2014 May 28.
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.
硝酰自由基（HNO）是一种潜在的心力衰竭治疗药物，已知其靶向半胱氨酸残基以形成亚磺酰胺和/或二硫化物。由于 HNO 衍生的修饰可能取决于其局部环境，我们研究了 HNO 在生理 pH 和温度下与半胱氨酸衍生物和 C 末端含半胱氨酸的肽的反应性。我们的研究结果表明，C 末端半胱氨酸的 HNO 衍生修饰的性质受 C 末端羧酸盐的影响。除了缺乏亚磺酰胺形成外，这些研究还揭示了新产物的存在，即磺羟肟酸衍生物（RS（O）2NHOH）和硫代磺酸盐（RS（O）2SR），推测在我们的实验条件下通过环状结构的中间产物形成，该环状结构水解生成亚磺酸（RSOH）。此外，这些修饰是在无氧的情况下形成的。
