| Project/Area Number |
04453153
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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 |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SUGIURA Yukio Institute for Chemical Research Kyoto University, Professor, 化学研究所, 教授 (40025698)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1993: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1992: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | enediyne / DNA cleavage / antitumor activity / esperamicin / calicheamicin / dynemicin / DNA conformation / molecular design / エスペラミシン / RNA切断 / コンホメーション選択的切断 / カリケミシン / C-1027 / DNA認識 / ビラジカル |
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| Research Abstract |
Enediyne antitumor antibiotics show novel molecular structures, afascinating action mode, and potent DNA cleaving activity. We clarified some characteristics of DNA strand scission by enediyne antibiotics such as esperamicin A_1, calicheamicin gamma_1 and dynemicin A.
(1) Double-stranded cleavage fashion : Of special interest is the fact that neocarzinostatin and C-1027 causes strand breaks two base pairs at specific sites in the two strands. This novel double-stranded cleavage fashion is different from that of esperamicin A_1 and calicheamicin gamma_1, which are found to have a three-bpseparation between cleavage sites on the two strands.
(2) Sequence-specific cleavage mode : Esperamicin A_1 and calicheamicin gamma_1 cleaved specifically at 5'-AGGA/TCCT sequences.
(3) Conformation-selective strand break : The cleavage sites by dynemicin A are observed at nucleotide residues near the bulge, mismatch, or nick sites. The result demonstrates conformation-dependence of DNA cleavage by dynemicin antibiotics.
These informations provide valuable implications for biological action of enediyne antitumor antibiotics and for molecular disign of new enediyne compounds.
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