期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 135, 期 20, 页码 7693-7704出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja401565w
关键词
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资金
- NIH [CA26731]
- MIT Center for Environmental Health Sciences [ES002109]
Nitrosothiols (RSNOs) have been proposed as important intermediates in nitric oxide (NO center dot) metabolism, storage, and transport as well as mediators in numerous NO. signaling pathways. RSNO levels are finely regulated, and dysregulation is associated with the etiology of several pathologies. Current methods for RSNO quantification depend on indirect assays that limit their overall specificity and reliability. Recent developments of phosphine-based chemical probes constitute a promising approach for the direct detection of RSNOs. We report here results from a detailed mechanistic and kinetic study for trapping RSNOs by three distinct phosphine probes, including structural identification of novel intermediates and stability studies under physiological conditions. We further show that a triarylphosphine-thiophenyl ester can be used in the absolute quantification of endogenous GSNO in several cancer cell lines, while retaining the elements of the SNO functional group, using an LC-MS-based assay. Finally, we demonstrate that a common product ion (m/z = 309.0), derived from phosphine RSNO adducts, can be used for the detection of other low-molecular weight nitrosothiols (LMW-RSNOs) in biological samples. Collectively, these findings establish a platform for the phosphine ligation-based, specific and direct detection of RSNOs in biological samples, a powerful tool for expanding the knowledge of the biology and chemistry of NO center dot-mediated phenomena.
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