2003 Fiscal Year Final Research Report Summary
Development of a Gene Expression Control Medicine and Analysis of the Interaction with a DNA Duplex.
| Project/Area Number |
14572012
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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) |
2002 – 2003
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| Keywords | Pyrrolepolyamide-nucleoside complex / Interaction of a DNA with a drug / Tm value / CD spectra / Stereoselective deuteration / (5'R)-[5'-^2H;5'-^<13>C]nucleoside |
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| Research Abstract |
Organic compounds capable of controlling gene expression by recognizing DNA sequence-specificity are expected to be viable gene therapy medicine. The nucleosides bearing pyrrolepolyamide which is minor groove binder were designed and synthesized as a lead compounds for gene therapy medicine and the analysis of DNA interaction with these compounds by Tm values and Circular Dichroism (CD) spectra was performed. In addition, the synthesis of {(5R)-D-[5-^2H_1;5-^<13>C]ribofuranosyl}nucleoside that is useful for structural analysis of conformation in DNA was carried out. 1.Deoxyguanosine bearing pyrrolepolyamide using 3-aminopropyl linker (GAP), using aminopropyonyl linker (GBP) and adenosine bearing pyrrolepolyamide (Apy) were synthesized. 2.The investigation of affinity for DNA duplexes by Tm values and CD spectra showed that DNA included the sequence of 5'-AAATT-3' with GAP complex has potential of highly selectivity as compare with complexes of other DNA. In this result, GAP might have usable sequence selectively in gene therapy, and provide possibility to be new series of antisense or antigene drugs. 3.Highly diastereoselective synthesis of {(5R)-D-[5-^2H_1;5-^<13>C]ribofuranosyl}thymine was established. A preparation of {(5R)-D-[5-^2H_1;5-^<13>C]ribose derivative of 1,2:5,6-di-O-isopropyliden-α-D-allofranose was successfully achieved by a ^<13>C Wittig reaction using Ph_3P^<13>CH_3I-BuLi to 5-oxoribose derivative and subsequent transformation into D-[5-^<13>C]ribose derivative with an AD reaction, selective acylation, oxidation with NaIO_4, and a stereoselective deuteride transfer reaction from Alpine-Borane-d to 5-oxo-D-[5-^<13>C]ribose derivative as the main reaction. {(5R)-D-[5-^2H_1;5-^<13>C]ribofuranosyl}thymine was synthesized in the established manner from this 5-^<13>C/^2H_1-double-labeled ribose.
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[Publications] Kawashima, E., Itoh, D., Kamaike, K., Terui, Y., Oshima, T.: "Synthesis and Analysis of Nucleosides Bearing Pyrrolepolyamide Binding to DNA."Nucleosides, Nucleotides & Nucleic Acids.. 22. 1309-1311 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ohba, Y., Kamaike, K., Terui, Y., Oshima, T., Kawashima, E.: "Design, synthesis and analysis of antiviral nucleosides bearing pyrrolepolyamide binding to nucleic acid (II):N^2- pyrrolepolyamidopropionylguanosine"Nucleic Acids Research Supplement. 29-30 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kawashima, E., Sekine, T., Umabe, K., Kamaike, K., Mizukoshi, T., Shimba, N., Suzuki, E., Kojima, C.: "New Sequential-Assignment Routes of Nucleic Acid NMR Signals Using A [5'-^<13>C]-Labeled DNA Dodecamer"Nucleosides, Nucleotides & Nucleic Acids.. 23. 255-262 (2004)
Description
「研究成果報告書概要(和文)」より
-
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[Publications] Kawashima, E., Itoh, D., Kamaike, K., Terui, Y., Oshima, T.: "Synthesis and Analysis of Nucleosides Bearing Pyrrolepolyamide Binding to DNA."Nucleosides, Nucleotides & Nucleic Acids. 22. 1309-1311 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ohba, Y., Kamaike, K., Terui, Y., Oshima, T., Kawashima, E.: "Design, synthesis and analysis of antiviral nucleosides bearing pyrrolepolyamide binding to nucleic acid (II) : N^2-pyrrolepolyamidopropionylguanosine"Nucleic Acids Research. Supplement. 29-30 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawashima, E., Sekine, T., Umabe, K., Kamaike, K., Mizukoshi, T., Shimba, N., Suzuki, E., Kojima, C.: "New Sequential-Assignment Routes of Nucleic Acid NMR Signals Using A [5'-^<13>C]-Labeled DNA Dodecamer"Nucleosides, Nucleotides & Nucleic Acids. 23(1&2). 255-262 (2004)
Description
「研究成果報告書概要(欧文)」より
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