| Project/Area Number |
03403009
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
無機・錯塩・放射化学
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
KURODA Reiko Univ. of Tokyo, Chemistry, Professor, 教養学部, 教授 (90186552)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Toru Univ. of Tokyo, Chemistry, Research Assistant, 教養学部, 助手 (40242036)
MATSUSHITA Nobuyuki Univ. of Tokyo, Chemistry, Research Assistant, 教養学部, 助手 (80219427)
錦織 紳一 東京大学, 教養学部, 助教授 (70134400)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥26,700,000 (Direct Cost: ¥26,700,000)
Fiscal Year 1993: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1992: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1991: ¥16,300,000 (Direct Cost: ¥16,300,000)
|
|---|
| Keywords | DNA / Metalloporphyrins / Chiral discrimanation / Induced CD / Molecular recognition / ポルフィリン錯体 / キラリティ- |
|---|
| Research Abstract |
The modes of DNA-porphyrin interactions are multiple and depend on the central metal ions. We have found that iron-tatrakis(4-N-methylpyridiniumyl)porphyrin possesses surprisengly high sequence preference towards the minor groove of three contiguous A.T base paris from DNase I footprinting study and affinity cleavage experiments. By analyzing CD in the porphyrins's Soret band induced by the interaction with chiral DNA, we could estimate the preferred binding modes and sequences semi-quantitatively.
A series of compounds which possess a second functional group at the end of a sidechain, as well as a compounds which possess a second functional group at the end of a sidechain, as well as a compound which substitutes a 4-N-methyl-pyridiniumyl by a tolyl group have been synthesized to study the origin of the sequence selectivity. Affinity cleavage experiments have shown that all the compounds exhibit the same high specificity and at maximum 3 positive charges are necessary for the recognition.
Molecular dynamics has shown that the most stable interaction is the side on model in the minor groove, then the major groove binding and the face on model in the minor groove. Non-bonded rather than Coulombic energy seems to contribute the stability difference.
A series of new complexes which contain a chiral ligand, [Cu(1,10-phenanthroline)(X-proline)]C1.3H_2O (X=D or L), have been synthesized and their DNA cleavage efficiency compared. The D-enantiomer cleaved DNA more efficiently than the L counterpart. The molecuar structure was determined by the single crystal X-ray diffractometry. A chiral amino acid, histidine, was introduced to the iron porphyrin. This is to study chiral recognition and the consequential difference in the DNA cleavage efficiency and base sequence specificity. The synthesis is near completion.
|
