1996 Fiscal Year Final Research Report Summary
Elucidation of structure of antitumor antibiotic kapurimycin A3 and reactivity toward DNA
| Project/Area Number |
07458142
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SAITO Isao Kyoto University, Faculty of Engineering, Professor, 工学研究所, 教授 (20026082)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Kazuhiko Kyoto University, Faculty of Engineering, Assistant Professor, 工学研究所, 助手 (70237303)
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| Project Period (FY) |
1995 – 1996
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| Keywords | kapurimycin A_3 / DNA alkylation / guanine N7 / antitumor antibiotic / epoxide / major groove |
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| Research Abstract |
Antitumor antibiotic kapurimycin A3, having a structure closely related to pluramycin family, alkylates DNA by the attack of the epoxide subunit on the guanine N7 to result in a formation of kapurimycin-DNA adduct. In order to know the factors responsible for such highly efficient and selective guanine alkylation, we have synthesized a series of truncated kapurimycin analogs as well as their epoxy alcohol and diol derivatives. DNA-cleaving activity examined by plasmid relaxation assay indicated that the ABC ring analog efficiently alkylates DNA,while the corresponding AB ring analog showed only a very weak DNA-cleaving activity. DNA cleavage experiments using ^<32>P-5'-end-labeled DNA fragment indicated that the sequence selectivity including 5'-side selectivity for 5'-GG-sequence was indistinguishable for kapurimycin A_3 and its ABC ring analog. We concluded that the ABC ring analog has a minimal structural unit for kapurimaycin A_3 to achieve effective and sequence specific guanine alkylation.
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