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|Title:||Chemical and biological properties of S-nitrosothiols|
|Authors:||Tullett, Jayne Margaret.|
|Presented at:||University of Leicester|
|Abstract:||Since its discovery, nitric oxide (NO) has been identified to influence a large number of physiological processes. This project examines S-nitrosothiols (RSNO) as pro-drugs of NO.;The overall aim of this project was to improve our present understanding of the chemical and biological properties of RSNOs. This project has demonstrated that under physiological conditions the stability of RSNOs varies with structure. Results have shown that S-nitrosocysteine and S-nitroso-L-cysteinylgylcine were the least stable of the RSNOs investigated, whereas S-nitroso-N-acetyl-L-cysteine, S-nitroso-3-mercaptopropionic acid and S-nitroso-2-mercapto-ethane sulphonic acid were the most stable. The decomposition of certain RSNOs is catalysed by trace amounts of copper. This phenomenon was particularly evident with the RSNOs, S-nitrosocysteine and S-nitroso-L-cysteinylglycine. Copper catalysed decomposition appears to occur more readily with RSNOs that allow the formation of a stable ring structure, in which Cu+ is bound to the nitrogen of the NO group and another electron-rich atom such as the nitrogen of an amino group. Copper catalysed the decomposition of S-nitrosoglutathione and S-nitroso-L--glutamyl-L-cysteine, but to a lesser extent. Investigations have shown that the decomposition of a stable RSNO is more rapid in the presence of a thiol which gives rise to an unstable RSNO via a transnitrosation reaction. In contrast, decomposition of an unstable RSNO is slower in the presence of a thiol which leads to the formation of a stable RSNO.;All RSNOs studied inhibited platelet aggregation and relaxed vascular smooth muscle in a dose dependent manner. In addition, all the RSNOs exhibited a dose-dependent inhibition of growth of A549 cells.;Generally no real correlation between the chemical and biological properties of RSNOs was observed.;It is clear that there are many factors controlling the release of NO from RSNOs which may have implications regarding the biological activity of these compounds.|
|Rights:||Copyright © the author. All rights reserved.|
|Appears in Collections:||Theses, MRC Toxicology Unit|
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