2005 Fiscal Year Final Research Report Summary
Natural products specifically inhibiting the cellular differentiation during echinoderm embryogenesisi
Project/Area Number |
15510176
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Living organism molecular science
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Research Institution | Nagahama Institute of Bio-Science and Technology (2004-2005) Hiroshima University (2003) |
Principal Investigator |
OHTA Shinji Nagahama Institute of Bio-Science and Technology, Faculty of Bioscience, Professor, バイオサイエンス学部, 教授 (60185270)
|
Co-Investigator(Kenkyū-buntansha) |
IKEGAMI Susumu Nagahama Institute of Bio-Science and Technology, Faculty of Bioscience, Professor, バイオサイエンス学部, 教授 (80011980)
|
Project Period (FY) |
2003 – 2005
|
Keywords | Actinomycete / Micromonospora sp. / Starfish embryos / Macrolide / Specific inhibitor / Thiomonospolide / Micromonospolide / Structure activity relationship |
Research Abstract |
Development of inhibitors against the formation of the modified histone heterodimer should lead to understand the relationship between the cellular differentiation and the formation of the modified histone heterodimer. We employed the following three-step screening to discover such inhibitors : the first step is a search for inhibitors against early gastrulation of starfish (Asterina pectinifera) embryos, the second step is a test for the formation of the modified histone heterodimer in the starfish embryo, and the third step is an assay for TGase inhibitor. Screening for more than 5,000 strains of microorganisms and for more than 500 species of marine sponges resulted in the isolation of a potent specific inhibitor designated as thiomonospolide as well as known macrolide, micromonospolide A, from a Micromonospora sp. The structure of thiomonospolide was elucidated on the basis of spectroscopic data. Thiomonospolide arrested the progression of embryonic development at the late blastula stage just prior to gastrulation of A.pectinifera. The minimum inibitory concentration of thiomonospolide was 1.0 μg/mL. Thiomonospolide inhibited the formation of crosslinked histone dimers during the midblastula stage of the starfish embryo at or above 1 μg/mL. Thiomonospolide strongly inhibited the activity of tissue transglutaminase. It is noteworthy that thiomonospolide inhibited potently V-ATPase activity.
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Author(s)
M.M.Konopleva, I.Matlawska, M.Wojcinska, A A.Ahmed, M.Rybczynska, A.Paszel, S.Ohta, T.Hirata, W.Bylka, T.J.Mabry, J.F Cannon
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Journal Title
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Description
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