Potential therapeutic uses for S-nitrosothiols.
The S-nitrosothiols (RSNOs) are thought to represent a circulating endogenous reservoir of nitric oxide (NO), and may have potential as donors of NO, distinct from currently used agents. They have the general formula RSNO, and naturally occurring examples include S-nitrosocysteine, S-nitrosoglutathione and S-nitrosoalbumin, in which R is an amino acid, polypeptide and protein respectively. RSNOs have anti-platelet properties, a theoretical role in the treatment of asthma and the potential to be used as agents to treat infectious diseases ranging from the common cold to AIDS. RSNOs are relatively unstable, being degraded to release NO and the corresponding disulphide. Their stability is influenced by the properties of the R group, heat, light, the presence of transition metal ions (in particular copper) and the presence of other thiols. RSNOs participate in transnitrosation reactions in which the -NO group is transferred to another thiol to form a more stable RSNO. Thus the stability of RSNOs in vivo is difficult to predict, and this has led to the development of more stable analogues, in which the properties of R are modified. Potential interactions of RSNOs include that with ascorbic acid (vitamin C), which enhances the ability of copper to catalyse their degradation. Transnitrosation reactions with thiol-containing enzymes can influence protein function, and the intracellular thiol glutathione, levels of which are influenced by many disease states, can also influence stability. Thus, although RSNOs have many theoretically useful properties, there are also many aspects of their biochemistry that need to be addressed before their therapeutic potential can be fully realized.
Richardson
G
G
Department of Clinical Pharmacology, William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, U.K.
Benjamin
N
N
D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000737:chemistry / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D026403:S-Nitrosothiols / Q000737:chemistry / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D000890:Anti-Infective Agents; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D026403:S-Nitrosothiols