2011 Fiscal Year Final Research Report
Creation of novel bioactive agents on the basis of fragment evolution approach of natural products
| Project/Area Number |
21603004
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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 |
Chemical biology
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| Research Institution | Yokohama City University |
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Principal Investigator |
OIKAWA Masato 横浜市立大学, 生命ナノシステム科学研究科・生命ナノシステム科学研究科, 教授 (70273571)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Ryuichi 北海道大学, 水産科学研究院, 教授 (20265721)
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| Project Period (FY) |
2009 – 2011
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| Keywords | グルタミン酸受容体 / リガンド / fragment evolution / 天然物 |
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| Research Abstract |
Development of novel ligands, that specifically interact with receptors located at synapses of mammalian nervous system, is important to understand and control complex brain functions at a molecular level. We had synthetically developed IKM-159 as a specific AMPA receptor antagonist, and in the present study, the structure-activity relationships have been extensively studied. As a result, we found that(2R)-IKM159 is neuronally active, whereas the(2S)-isomer is inactive. Furthermore, the interactions with GluA2 subunit have been clarified by X-ray crystallography of(2R)-IKM159 in complex with GluA2 dimer.
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