2005 Fiscal Year Final Research Report Summary
Structure of Molecular Assembles of Bioactive Natural Products Formed in Biomembranes
| Project/Area Number |
15201048
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
MURATA Michio Osaka university, Chemistry, Professor, 理学研究科, 教授 (40183652)
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| Co-Investigator(Kenkyū-buntansha) |
OISHI Tohru Osaka university, Chemistry, Associate Professor, 理学研究科, 助教授 (90241520)
MATSUMORI Nobuaki Osaka university, Chemistry, Assistant Professor, 理学研究科, 助手 (50314357)
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| Project Period (FY) |
2003 – 2005
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| Keywords | amphotericin B / solid state NMR / antibiotics / self assemble / molecular aggregate / ergosterol / polyene antibiotics |
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| Research Abstract |
Amphotericin B (AmB) is known to assemble together and form an ion channel across biomembranes. The selective toxicity is generally accounted for by its higher affinity for ergosterol than cholesterol. To better understand the ion-channel structure and intermolecular interactions, we prepared various AmB derivatives and measured their activities. AmB dimers which are covalently linked between the amino groups by short chains showed more potent ion-channel activity than that of AmB, indicating that the mutual topology of AmB molecules is a head-to-head orientation. AmB-sterol conjugates were also designed and examined for ion-channel activities. AmB-ergosterol conjugates showed more powerful ion-channel activity than AmB-cholesterol congeners, suggesting that stronger van der Waals interaction between AmB and ergosterol contributes to the higher ion-channel activity. Finally, we prepared conformation-restricted derivatives of AmB, in which the amino and carboxyl groups were bridged with various lengths of alkyl chains. The derivatives successfully gave us information on the active-conformation of the sugar moiety of AmB in membrane. These derivatives are now labeled by ^<13>C and/or ^<19>F to probe the molecular structure of AmB ion channel using solid-state NMR.
The mode of membrane permeabilizing action of amphidinols, dinoflagellate-originating polyene-polyhydroxy compounds, was investigated mainly by NMR methods. The polyhydroxy and polyolefinic parts play roles in the formation of ion channel lining and in binding in the membrane. Detailed NOE measurements in membrane-mimicking systems elucidated that the central part of amphidinols takes a hairpin conformation, which should be, at least in part, accounted for their strong biological activities.
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Research Products
(26 results)
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[Journal Article] Hairpin conformation of amphidinol possibly accounting for potent membrane permeabilizing activities.2005
Author(s)
Houdai, T., Matsuoka, S., Morsy, N., Matsumori, N., Satake, M., Murata, M.
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Journal Title
Tetrahedron 61
Pages: 2795-2802
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Isolation and structure elucidation of a new amphidinol with a truncated polyhydroxyl chain from Amphidinium klebsii.2005
Author(s)
Morsy, N., Matsuoka, S., Houdai, T., Matsumori, N., Adachi, S., Murata, M., Iwashita, T., Fujita, T.
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Journal Title
Tetrahedron. 61
Pages: 8606-8610
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] An Amphotericin B-ergosterol covalent conjugate with powerful membrane permeabilizing activity.2004
Author(s)
Matsumori, N., Eiraku, N., Matsuoka, S., Oishi, T., Murata, M., Aoki, T., Ide, T.
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Journal Title
Chem.Biol. 11
Pages: 673-679
Description
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