| Project/Area Number |
16350086
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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 |
Chemistry related to living body
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| Research Institution | Nagoya University |
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Principal Investigator |
HAYAKAWA Yoshihiro Nagoya University, Graduate School of Information Science, Professor, 大学院情報科学研究科, 教授 (50022702)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Masaki Nagoya University, Graduate School of Information Science, Research Associate, 大学院情報科学研究科, 助手 (10362295)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2004: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | antisense nucleic acid / oligonucleotide / c-di-GMP / biofilm / immune enhancer / Staphylococcus aureus / Pseudomonas aeruginosa / biofilm-forming bacterial infection / バイオフィルム感染症治療薬 / 免疫活性化剤 / 免疫応答活性化 / 抗がん剤 / ヌクレオチド / ユニバーサル塩基 / 鉄還元菌 / 抗がん作用 / アミダイト法 / カルボン酸 / 促進剤 |
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| Research Abstract |
(1) We developed a new strategy for the stereoselective preparation of dideoxyribonucleoside phosphorothioates with the (R) or the (S) configuration at the stereogenic phosphorus atom, and, based on this strategy, achieved the synthesis of oligodeoxyribonucleotides with stereochemically pure phosphate/phosphorothioate chimeric backbones, which are important compounds for antisense chemotherapy.
(2) We developed new methods for the synthesis of c-di-GMP and its various analogs; these methods are capable of providing target compounds in large amounts, such as hundreds of milligrams to several grams. The synthesis allowed us to carry out extensive investigations of the biological activities of c-di-GMP and its analogs. As a result, we found that c-di-GMP appears to act as a second messenger in bacteria and shows a variety of important bioactivities. Among them, the particularly attractive one is the regulation of biofilm formation and infection to host cells by various bacteria; that is, inhibition of biofilm formation of S. aureus, P. aeruginosa and E. coli; reduction of infection of S. aureus to HeLa cells; reduction of the virulence of biofilm-forming S. aureus strains in a mouse model of mastitis infection in vivo; and activation of immune response. Further, it was disclosed that c-di-GMP inhibits basal and growth factor-stimulated human colon cancer cell proliferation.
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