| Project/Area Number |
11101001
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
HAYAKAWA Yoshihiro Nagoya University, Graduate School of Human Informatics, Dr. Sc., 大学院・人間情報学研究科, 教授 (50022702)
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| Co-Investigator(Kenkyū-buntansha) |
SEKINE Mitsuo Tokyo Institute of Technology, Department of Life Science, Dr. Sc., 大学院・生命理工学研究科, 教授 (40111679)
MAKINO Keisuke Kyoto Univeristy, International Innovation Center, Dr. Sc., 国際融合創造センター, 教授 (50159141)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥176,400,000 (Direct Cost: ¥165,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2001: ¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2000: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1999: ¥77,000,000 (Direct Cost: ¥77,000,000)
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| Keywords | phosphoramidite method / allyl protection / CMP-Neu5Ac / acid / azole complex / oxanosine / telomere / H-phosphonate method / N-acylated DNA / ヌクレオチド化学合成 / CMP-New5Ac / アンチセンス核酸 / デオキシオキザノシン / 2-5A / 一酸化窒素 / RNAオリゴマー / 遺伝子傷害 / クロスリンク / N-アシルDNA / 塩基対形成能 / 分子認識能 / 塩基部無保護アミダイト法 / 修飾DNAオリゴマー / アリル保護アミダイト法 / DNA-ペプチドコンジュゲート / 一酸化窒素による発ガン / 塩基配列認識ペプチド |
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| Research Abstract |
Hayakawa has developed efficient solid-phase synthesis of DNA and RNA oligomers via the phosphoramidite method using an acid/azole complex as the promoter. He has also invented a novel phosphoramidite method with molecular sieves as a moisture scavenger, allowing the solution-phase preparation of short oligonucleotides by the use of stoichiometric amounts of starting materials and a promoter. These new approaches have allowed highly efficient synthesis of biologically attractive/important substances such as CMP-Neu5Ac, 2-5A core, c(GpGp), DNA-peptide conjugates, and oligodeoxyribonucleotides with S-acetyl-2-thioethyl triester backbone. Makino has studied to elucidate unsolved nucleic acids structures and its relevance to biological functions. He (1) has established complete mechanisms for all the base damage by nitric oxide and their relevance to cancer and cell death, (2) has found varied isomeric structures of i-motif of C-repeat in human telomere and suggested its relationship with cancer and cell death, (3) has elucidated the relationship between the chirality in phosphorothioate antisenses and their target DNA and RNA recognition ability, and (4) has developed the novel method for peptide library for given base sequences. Sekine has found that a serious side reaction associated with oligonucleotide synthesis in the H-phosphonate approach occurs owing to an intramolecular attack of the 5'-terminal hydroxyl group of the growing chain on the closest internucleotidic phosphoryl group. Based on this finding, an improved H-phosphonate approach using active ester intermediates has been developed. The "proton-block method" as a new strategy for the synthesis of DNA fragments without base protection and post-treatment has been also explored. This strategy was utilized for an innovative route to N-acylated DNA fragments which have proved to have sufficient base-pairing ability.
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