1997 Fiscal Year Final Research Report Summary
Preparation of Artificial Ribonucleases and Their Applications to the Therapy for Cancer and AIDS
| Project/Area Number |
08559005
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
広領域
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| Research Institution | Graduate School of Engineering, The University of Tokyo |
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Principal Investigator |
KOMIYAMA Makoto Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Professor., 大学院・工学系研究科, 教授 (50133096)
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| Co-Investigator(Kenkyū-buntansha) |
SUMAOKA Jun Department of Chemistry and Biotechnology, Graduate School of Engineering, The U, 大学院・工学系研究科, 助手 (10280934)
YASHIRO Morio Department of Chemistry and Biotechnology, Graduate School of Engineering, The U, 大学院・工学系研究科, 助教授 (30192785)
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| Project Period (FY) |
1996 – 1997
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| Keywords | RNA / Hydrolysis / Oligoamine / Artificial ribonuclease / Cancer / AIDS / Therapy |
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| Research Abstract |
With the aims to develop new therapeutic methods for cancer and AIDS,artificial ribonucleases have been prepared, and RNA scission mechanism is investigated. It is confirmed that intramolecular acid/base cooperation is responsible for the remarkable catalysis of oligoamines for RNA hydrolysis. Novel artificial ribonucleases in which oligoamines are attached inside of DNA oligomers (which are complementary with a part of the substrate RNA) have been synthesized. These artificial enzymes cut the target RNA more precisely than the ones with the scissors at the ends of DNA oligomers, mainly because the scissors are fixed in the rigidly structured double strands. Furthermore, Conjugates of an intercalator and either glycine or iminodiacetate show effective scission of RNA.These conjugates are neutral or negatively charged, which is highly in contrast with the fact that the previously reported RNA scissors are positively charged. Thus, they can be placed exactly at the desired site, even in a strong electrostatic field induced by RNA.These artificial ribonucleases cleave only the target RNA in cells, and thus should be highly potent for the therapy of cancer and AIDS.
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