|Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
Nucleic acids (DNA,RNA) play important roles in transmission of essential genetic imformation in living cell. The oxidation of nucleic acids and related compoiunds by reactive oxygen species, such as hydrogen peroxide, hydroxy radical, superoxide anion, singlet oxygen, have recently been receiving much attention as they may be involved in mutagenesis, carcinogenesis and aging. On the other hand, protection against the damage and repairing of the damaged nucleic acids are seemed to be one of the vital inherent functions. We focused on oxidative damage and reductive repair of nucleic acids and related compounds from a chemical point of view and found following seceral remarkable results and some imformation.
1. Oxidation of pyrimidine bases, especially thymidine derivatives were investigated and structures of oxidation products were elucidated. Thus, thymidine derivatives were transformed into the epoxide with mcpba and into ring contracted imidazolone derivatives with superoxide ion. A p
lausible mechanism was also presented. 2. Reaction of 1,3-dimethylthymine or thymidine epoxide with seceral amines and L-amino acid derivatives as a model reaction for nucleic acid-protein cross links was studied and the stereo-structures of the products were elucidated on the bases of chemical isomerization reaction, X-ray analysis and the specific rotation. 3. The bromhydrins, which were oxidatively damaged products of thymidine derivatives, were repaired with sunlight or heat via radical mechanism to regenerate the parent thymidine derivatives. A novel one-electron transfer system consisting of 1,5-dihydro-5-deazaflavin and flavin could be applicable to this reparing system under milder conditions. Furthermore, the bromohydrins were effectively reduced with a system of Cu(II)-ascorbic acid or with using coenzyme models, 1,5-dihydro-5-deazaflavin, 1,4-dihydroquinoline, in the presence of acid additive. 4. The diol of the thymidine derivatives, another type of oxidatively damaged product, was effectively converted to reduced original product with the phosphite reagent. 5. The adenine-1-oxide derivatives, the other oxidatively damaged components of nucleic acid, were reductively repaired by reduced form glutathione under irradiation with sunlight to give the corresponding adenine derivatives. Less