1999 Fiscal Year Final Research Report Summary
Studies of neighboring base damage induced by oxidation of synthetic DNAs containing oxidatively damaged bases
| Project/Area Number |
10671979
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Osaka City University (1999)
Hokkaido University (1998) |
|---|
Principal Investigator |
INOUE Hideo Osaka City University, Faculty of Engineering, department of Bioapplied Chemistry, 工学部, 教授 (80088856)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | DNAs containing damaged bases / 8-oxoguanine / 8-oxoadenine / KMnOィイD24ィエD2 oxidation / neighboring base damage / reaction mechanism |
|---|
| Research Abstract |
Recently we found that KMnOィイD24ィエD2 oxidation of DNA oligomers containing a 7,8-digydro-8-oxoguanine (8-oxo-G) residue induces damage to the neighboring base residues. The present data from several experiments suggested that a redox reaction involving the 8-oxo-G initiates damage: the reactivity of the DNA bases at the site 5'-adjacent to the 8-oxo-G was in the order G > A > T, C, and this preference correlates with the electron donating abilities of the bases. The present study also indicated that other oxidatively damaged bases, 7,8-dihydro-8-oxoadenine (8-oxo-A), 5-hydroxyuracil (5-oh-U) and 5-hydroxycytosine (5-oh-C) show similar behavior in DAN. On the other hand, in order to examine the pathways and the intermediates for the oxidative degradation of 8-oxo-G and 8-oxo-A, we have carried out the KMnOィイD24ィエD2 oxidation using 8-oxo-2'-deoxy-guanosine and -adenosine derivatives as a model. The reactions gave three major products, respectively, and we have determined the structures of the products. Based on the structures, we deduced active oxidation intermediates from the 8-oxo-purines (in DNA) which may be involved in the redox reaction as electron acceptors.
|
