The aim is to investigate the stereochemistry of thiol-disulfide interchanges in order to understand better their role in biological processes, especially protein folding, radiation protection and carcinogenesis. These studies will be extended to the selenol/diselenide interchanges also. Extensive computer searches of the small molecule and protein crystallographic data banks will be carried out for finding out short non-bonded contacts to sulfur and selenium and the preferred directions of approach of sulfur and selenium to other atoms or chemical groups. The crystal structures and charge densities of thiols selenols, sulfides, selenides, mixed sulfines, disulfides and selenol trisulfides will be studied using x-ray diffraction. By analyzing the short non-bonded atomic contacts to sulfur and selenium in terms of the chemical and electronic nature of sulfur and selenium and their adjacent and contacting atoms or chemical groups, a stereochemical picture of the reaction path or paths for thiol-disulfinde will be developed. Small oligopeptides containing two and three thiols will be synthesized and the formation of disulfide and their interaction with thiol groups will be studied in solution and solid states. Using all this information, proposals for the role of this important reaction in biological processes such as protein folding, radiatiion protection and carcinogenesis will be developed and evaluated. Chemical agents that protect against radiation by thiol-disulfinde interchanges will be studied and criteria which will be of some help for designing anti-radiation agents will be developed.
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