2006 Fiscal Year Final Research Report Summary
Creation and efficient synthesis of nucleic acids and related compounds with valuable functionality and bioactivity
| 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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| Keywords | antisense nucleic acid / oligonucleotide / c-di-GMP / biofilm / immune enhancer / Staphylococcus aureus / Pseudomonas aeruginosa / biofilm-forming bacterial infection |
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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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[Journal Article] Bacterial c-di-GMP is an Immunostimulatory Molecule.2007
Author(s)
D.K.Karaolis, T.K.Means, D.Yang, M.Takahashi, T.Yoshimura, E.Muraille, D.Philpott, J.T.Schroeder, M.Hyodo, Y.Hayakawa, B.G.Talbot, E..Brouiliette, F.Malouin
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Journal Title
J. Immunology 178・8
Pages: 2171-2181
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Bacterial c-di-GMP is an Immunostimulatory Molecule.2007
Author(s)
D.K.Karaolis, T.K.Means, D.Yang, M.Takahashi, T.Yoshimura, E.Muraille, D.Philpott, J.T.Schroeder, M.Hyodo, Y.Hayakawa, B.G Talbot, E.Brouiliette, F.Malouin.
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Journal Title
J. Immunology 178
Pages: 2171-2181
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis(3'-5')-cyclic di-GMP in virulence.2006
Author(s)
H.Kulesekara, V.Lee, A.Brencic, N.Liberati, J.Urbach, S.Miyata, D.G.Lee, A.N.Neely, M.Hyodo, Y.Hayakawa, F.M.Ausubel, S.Lory
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Journal Title
Proc. Natl. Acad. Sci. U.S.A. 103・8
Pages: 2839-2844
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis(3'-5')-cyclic di-GMP in virulence.2006
Author(s)
H.Kulesekara, V.Lee, A.Brencic, N.Liberati, J.Urbach, S.Miyata, D.G Lee, A.N.Neely, M.Hyodo, Y.Hayakawa, F.M.Ausubel, S.Lory.
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Journal Title
Proc. Natl. Acad. Sci. U.S.A. 103
Pages: 2839-2844
Description
「研究成果報告書概要(欧文)」より
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