Forum: therapeutic applications of reactive oxygen and nitrogen species in human diseaseBiological chemistry and clinical potential of S-nitrosothiols
Introduction
S-Nitrosothiols are compounds with the generic structure R-SNO. Older, chemical, literature refers to these compounds as thionitrites, but the name ‘S-nitrosothiol’ is now more popular and will be used in this review. Nitrosothiols were first synthesized as early as 1840 [1], and were used in biomedical research in the 1970s and 1980s. As is true for many aspects of nitric oxide biology, the chemistry of S-nitrosothiols, which was sporadically, yet expertly, examined by aficionados for many years, is now directly relevant to the biology of vascular homeostasis, neurotransmission and inflammation.
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Synthesis
Most S-nitrosothiols can be synthesized from the reaction between parent thiol and acidified nitrite (, , where RSH represents a thiol and RSNO an S-nitrosothiol). Acidification of a mixture of thiol and sodium nitrite results in the development of color, indicative of S-nitrosothiol formation. The color is usually in the orange-red region, however there are exceptions. For example S-nitroso-N-acetyl penicillamine (SNAP) is purple/green. As many biologically
Biological functions of S-nitrosothiols
Any discussion of the roles of S-nitrosothiols in vivo can be divided into two major concepts: (i) How do exogenously added S-nitrosothiols affect cellular functions?, and (ii) do biological systems use endogenous S-nitrosothiols to control biological responses?
The biological activities of S-nitrosothiols were realized before the landmark discovery that nitric oxide was an endogenously generated molecule [42], [43]. Data obtained using S-nitrosothiols contributed to discerning the identity of
Concluding remarks
S-Nitrosothiols are endogenous compounds that appear to play a role in signal transduction and stress responses. In addition, these compounds have a multitude of pharmacological effects, many of which have immediate clinical corollaries. The development of new bioactive compounds and the development of methodologies to examine both endogenous and exogenous S-nitrosothiols are the driving forces that will no doubt propel these multifaceted agents into the clinical arena.
Acknowledgements
The author would like to thank Drs. B. Kalyanaraman, Victor Darley-Usmar, Ravinder Singh, Eugene Konorev, and Rakesh Patel for insightful and stimulating discussions on the subject of S-nitrosothiols. The author would also like to acknowledge the support of the National Institutes of Health grants GM55792 and RR01008.
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Neil Hogg is an Associate Professor in the Biophysics Research Institute of the Medical College of Wisconsin, Milwaukee. He received his Ph.D. in 1993 from the University of Essex, Colchester, UK, under the joint supervision of Dr. Mike Wilson (University of Essex) and Dr. Victor Darley-Usmar (Wellcome Research Laboratories, Beckenham, Kent, UK). Upon hearing the news that Mike Holmgren had become head coach of the Green Bay Packers he headed to Milwaukee to work as a postdoc’ for Dr. Raman Kalyanaraman, and became an Assistant Professor in 1997. His current interests include the role of S-nitrosothiols in biological systems, the biological chemistry of peroxynitrite, the antioxidant behavior of nitric oxide, and the formation of superoxide by nitric oxide synthase isoforms. Despite this year’s 8 and 8 record, he has no plans to move to Seattle.