1995 Fiscal Year Final Research Report Summary
Novel metal complex oligomer which forms triple helix with DNA
| Project/Area Number |
06453046
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Inorganic chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KURODA Reiko Univ.of Tokyo, College of Arts and Sciences, Chemistry, Professor, 教養学部, 教授 (90186552)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Toru Univ.of Tokyo, College of Arts and Sciences, Chemistry, Research Assistant, 教養学部, 助手 (40242036)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Triple helix / Base sequences / Metal complexes / Chirality / CD spectroscopy |
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| Research Abstract |
DNA triple helix formation is a unique and an attractive approach towards the control of gene expression and DNA replication. Triple helices are formed by binding a single stranded DNA to a double helical DNA.This is in contrast to the case of antisense RNA/DNA which requires a single stranded nucleic acid target. Triple helix formation is highly sequence selective, however, it is limited to DNA of homopurine-homopyrimidine sequences. To overcome this limitation, we have investigated novel oligomer compounds which on polymerization form a triple helix with a double stranded DNA of general base sequence.Such oligomeric units can be metal complexes, although formation of a smooth backbone in the DNA groove may be problematic in this case. In this project we have designed a novel nucleotide analogue wihch potentially discriminates one particular DNA base from others and can be incorporated into a single stranded DNA.Prior to synthesis, the sequence recognizing ability of the compound was checked by computer modeling and force field calculations. Synthesis of the compound is underway. Additionally, to understand the binding mode of metal complexes in the DNA grooves, copper complexes with chiral ligands have been studied. Ligand binding to DNA was estimated through intrinsic DNA cleaving ability. A method for obtaining quantitative information on the binding of metalloporphyrins to DNA has also been developed based on induced CD spectroscopy.
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