2006 Fiscal Year Final Research Report Summary
Synthesis of bacterial peptidoglycan fragments for elucidation of the immunostimulatory function and for aplication as immune adjuvant
| Project/Area Number |
17510178
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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 |
Living organism molecular science
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIMOTO Yukari Osaka University, Graduate School of Science, Department of Chemistry, Associate Professor, 大学院・理学研究科, 講師 (00362616)
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| Project Period (FY) |
2005 – 2006
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| Keywords | peptidoglycan / innate immunity / glycoconjugate / immune adjuvant / fluorescence-label |
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| Research Abstract |
Bacterial cell wall component, peptidoglycan (PGN), has been known as a potent immunostimulator and an immune adjuvant. In order to elucidate the recognition mechanism of PGN by its receptors such as Nod1, Nod2 and also Toll like receptor (TLR) 2, we synthesized the partial structures of PGN and the fluorescence-labeled compounds. The synthetic methods to construct the glycan-peptide structures were also developed.
For the investigation of Nod1 recognition, we synthesized the ligands, four optical isomers of γ-D-glutamyl-diaminopimelic acid (iE-DAP) using three optical isomers of DAP separated with chiral HPL C. The Nod1 stimulatory activities were obtained, and it was shown that the differences of the activities of four isomers. Based on this result, we developed the new synthetic method to obtain most stimulatory native meso-DAP and iE-meso-DAP. The fluorescence-labeled iE-DAP were also synthesized and succeeded in obtaining the labeled compound which kept the Nod1 stimulating activity. We also prepared the fluorescence-labeled Nod2 ligands, muramyl dipeptide (MDP), for the elucidation of Nod2 stimulation mechanism.
The PGN fragment, MDP has immune adjuvant activity, and we planed to apply its activity to a synthetic vaccine with making covalent connection between the adjuvant and antigen via a carrier protein. For the introduction of the immune' adjuvant to the complex, we developed the method to introduce the linker to the PGN fragments and succeded to obtain several immunostimulatory compounds including 6-O-acyl-MDP with the linker.
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Research Products
(24 results)
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[Journal Article] Synthesis of peptidoglycan fragments and evaluation of their biological activity.2006
Author(s)
Inamura, S., Fujimoto.Y., Kawasaki, A., Shiokawa, Z., Woelk, E., Heine, H., Lindner, B., Inohara, N., Kusumoto, S., Fukase, K.
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Journal Title
Org.Biomol.Chem. 4
Pages: 232-242
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments.2006
Author(s)
Hasegawa, M., Yang, K., Hashimoto, M., Park, J.-H., Kim, Y.-G., Fujimoto, Y., Nunez, G., Fukase, K., Inohara, N.
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Journal Title
J.Biol.Chem. 281
Pages: 29054-29063
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes.2006
Author(s)
Tanabe, T., Ishige, I., Suzuki, Y., Aita, Y., Furukawa, A., Ishige, Y., Uchida, K., Suzuki, T., Takemura, T., Ikushima, S., Oritsu, M., Yokoyama, T., Fujimoto, Y., Fukase, K., Inohara, N., Nunez, G., Eishi, Y.
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Journal Title
Biochim.Biophys.Acta 1762
Pages: 794-801
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Meso-diaminopimelic acid and meso-lanthionine, amino acids specific to bacterial peptidoglycans, activate human epithelial cells through NOD1.2006
Author(s)
Uehara, A., Fujimoto.Y., Kawasaki, A., Kusumoto, S., Fukase, K., Takada, H.
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Journal Title
J.Immunol. 177
Pages: 1796-1804
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Toll-like receptors, NOD1 and NOD2, in oral epithelial cells.2006
Author(s)
Sugawara, Y., Uehara, A., Fujimoto.Y., Kusumoto, S., Fukase, K., Shibata, K., Sugawara, S., Sasano, T., Takada, H.
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Journal Title
J.Dent.Res. 85
Pages: 524-529
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A synthetic peptidoglycan fragment as a competitive inhibitor of the melanization cascade.2006
Author(s)
Park, J.W., Je, B-R., Piao, S., Inamura, S., Fujimoto, Y., Fukase, K,.Kusumoto, S., Soderhall, K., Ha, N.-C., Lee, B.L.
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Journal Title
J.Biol.Chem. 281
Pages: 7747-7755
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo.2006
Author(s)
Masumoto, J., Yang, K., Varambally, S., Hasegawa, M., Tomlins, S.A., Qui, S., Fujimoto.Y., Kawasaki, A., Foster, S.J., Horie, Y., Mak, T.W., Nunez, G., Chinnaiyan, A.M., Fukase, K., Inohara, N.
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Journal Title
J.Exp.Med. 203
Pages: 203-213
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.2005
Author(s)
Cho, J.H., Fraser, I.P., Fukase, K., Kusumoto, S., Fujimoto, Y., Stahl, G.L., Ezekowitz, R.A.B.
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Journal Title
Blood 106
Pages: 2551-2558
Description
「研究成果報告書概要(欧文)」より
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