| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
|
|---|
| Research Abstract |
Recently, reactions of natural products and their derivations toward DNA have been actively investigated. These researches provide molecular recognition of organic compounds toward DNA as well as structures and functions of DNA. Furthermore, this knowledge provides not only molecular mechanism of antitumor agents targetting DNA but also fundamental information to the cancer research.
Ptaquiloside is a potent carcinogenic compound isolated from the bracken fern Pteridium aquilinum var. latiusculum. The bracken ultimate carcinogen generated from under weakly basic conditions acts as a powerful alkylating agent toward amino acids and nucleic acid bases, and causes cleavage of DNA. Using deoxytetranucleotide d(GTAC), we disclosed the molecular mechanism of DNA cleavage with the ultimate carcinogen : i) the bracken ultimate carcinogen forms covalent adducts through N-3 of adenin or N-7 of guanine in DNA with opening of the cyclopropane ring, ii) spontaneous cleavage of the N-glycosidic linkage occurs primarily at the modified adenines to produce abasic sites, and iii) the abasic sites are so unstable that subsequent backbone breakage occurs via a b-elimination reaction.
We designed and synthesized simpler analogs of the bracken ultimate carcinogen, and found that these analogd are much more stable than the bracken ultimate carcinogen and possesses DNA cleaving activity comparable to that of the bracken ultimate carcinogen.
A tribromoacetamide, isolated from a marine alga, exhibits a growth-inhibitory against a marine bacterium with an adhering property. We have found that tribromoacetamides have cytotoxicity, and studied of structure-cytotoxicity relationships. Furthermore, tribromoacetamides proved to be an inhibitor of tubulin-polymerization.
|
