Mechanism-Based Triarylphosphine-Ester Probes for Capture of Endogenous RSNOs
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Seneviratne_2013-Mechanism-based triarylphosphine.pdf
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Author(s)
Wishnok, John S.
Wogan, Gerald N.
Seneviratne, Uthpala I.
Godoy, Luiz Claudio
Tannenbaum, Steven Robert
Date Issued
April 2013
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Seneviratne, Uthpala, Luiz C. Godoy, John S. Wishnok, Gerald N. Wogan, and Steven R. Tannenbaum. “Mechanism-Based Triarylphosphine-Ester Probes for Capture of Endogenous RSNOs.” Journal of the American Chemical Society 135, no. 20 (May 22, 2013): 7693-7704. © 2013 American Chemical Society
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Final published version
Abstract
Nitrosothiols (RSNOs) have been proposed as important intermediates in nitric oxide (NO[superscript •]) 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[superscript •]-mediated phenomena.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/ja401565w
