Development of the Efficient Synthetic Method for Nucleosides labeled with Stable Isotopes and Their Application to Structural Analysis of the Complex of a DNA with a Drug
| Project/Area Number |
11672117
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
KAWASHIMA Etsuko Tokyo University of Pharmacy and Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (30057343)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | nucleosides labeled with Stable Isotopes / complex of a DNA with a drug / [5'-^<13>C]nucleoside / highly diastereoselectiv (2'R)-2'-deoxy [2-^2H]guanosine / D-[5-^2H]ribofuranose / 標識DNA / distamycin誘導体の認識 / [5'-^2H_1][5'-^<13>C]ヌクレオシド / 高ジアステレオ選択的 / (2'R)-2'-デオキシ[2'-^2H]グアノシンの合成 / 票識DNAと医薬品の複合体 |
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| Research Abstract |
For the elucidation of the recognition mechanism of a DNA with a drug, the studies were performed as follows ; 1. the structural analysis of the complex of a [5'-^<13>C]DNA with Tallimustine (distamycin analogue) by NMR spectroscopy and 2. the development of the efficient methodology for the synthesis of 2'-deoxyribonucleosides site-specifically and diastereoselectivly labeled with ^<13>C and/or ^2H at their 5'- or 3'-positions. On the first study, the analysis of a d(C^*G^*C^*G^*A^*A^*T^*T^*C^*G^*C^*G)_2 {N^* : [5'-^<13>C]nucleotide} provided us with the correlation between C5'(i)-C6H(i-1) or -C8H(i), the sequential NOEs and unambiguous assignment of all the signals. We extend these results to NMR study of the complex of [5'-^<13>C]DNA with Tallimustine (distamycin analogue). The structural information on surrounded by H5' protons in a complex of these drug with a DNA has not been obtained, because of the difficulty of the assignment for H5' proton signals. We have overcome this problem by NMR analysis of a complex of [5'-^<13>C]DNA with a drug. Information obtained from our studies should aid in the investigation of sequence-specific DNA-protein or -drug recognition processes.
On the second studies, we achieved the development of the efficient methodology for the synthesis of (2'R)-2'-deoxy[2-^2H]guanosine and D-[5-^2H]ribofuranose derivative. Moreover, we found that a significant role of the phenylcarbamoyl protecting group in the asymmetric dihydroxylation reaction of the unsubstituted allyl alcoholic system using AD-mix-α and -β was confirmed to afford remarkably high enantioselectivity (>99% ee).
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Report
(3 results)
Research Products
(9 results)
