Design and synthesis of kainoid-type molecular probes for elucidation of the mechanism of allodynia induction

Research Project

Project/Area Number	24310154
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Partial Multi-year Fund
Section	一般
Research Field	Living organism molecular science
Research Institution	Gifu University
Principal Investigator	FURUTA Kyoji 岐阜大学, 医学(系)研究科(研究院), 准教授 (40173538)
Co-Investigator(Renkei-kenkyūsha)	MINAMI Toshiaki 大阪医科大学, 医学研究科, 教授 (00257841) DOI Hisashi 理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (00421818)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000) Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000) Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000) Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords	アロディニア / 神経障害性疼痛 / アクロメリン酸 / カイノイド / 分子プローブ / グルタミン酸受容体 / 受容体 / カイニン酸
Outline of Final Research Achievements	Several kainoid-type analogs were designed and synthesized for the purpose of identifying a novel receptor involved in the induction and maintenance of allodynia, a major symptom of neuropathic pain. Efficient synthetic methods to selectively modify the individual substituents attached to the pyrrolidine-ring skeleton of kainoids were established, making it possible to easily prepare kainoid analogs with a variety of substituents. Evaluation of the synthetic kainoids for allodynia-inducing/suppressing activity and binding affinity for glutamate receptors specified some promising analogs as biochemical tools. The existence of a novel activation mechanism of kainate receptor was also suggested.