Nitroxyl (HNO) donors exhibit promising pharmacological characteristics for treatment of cardiovascular disorders, cancer and alcoholism. However, whether HNO also serves as an endogenous signaling agent is currently unknown, largely due to the inability to selectively and sensitively detect HNO in a cellular environment. Although a number of methods to detect HNO have been developed recently, sensitivity and selectivity against other nitrogen oxides or biological reductants remain problematic. To improve selectivity, the electrophilic nature of HNO has been harnessed to generate modifications of thiols and phosphines that are unique to HNO, especially compared to nitric oxide (NO). Given high bioavailability, glutathione (GSH) is expected to be a major target of HNO. As a result, the putative selective product glutathione sulfinamide (GS(O)NH2) may serve as a high yield biomarker of HNO production. In this work, we describe a method to detect GS(O)NH2 with nanomolar sensitivity, even in the presence of GSH and derivatives.

Analysis of an intracellular biomarker following exposure to therapeutic levels of nitroxyl (HNO) donors

248th National Meeting (2014)

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