Identification of the target molecule of bis-acetylenic alcohols which inhibit the lymphangiogenesis

Research Project

Project/Area Number	15K08026
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Drug development chemistry
Research Institution	Kyushu University
Principal Investigator	Miyamoto Tomofumi 九州大学, 薬学研究院, 准教授 (40182050)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	リンパ管新生阻害 / ビスアセチレンアルコール / 標的分子探索 / 磁気ビーズ / 細胞増殖阻害 / リンパ管新生 / 標的分子 / テトラアセチレンアルコール / ビスアセチレン / トリスアセチレン / クリックケミストリー
Outline of Final Research Achievements	The bisacetylenic alcohols have been discovered from a marine sponge (Callyspongia sp.) at Iriomote-island, Okinawa Prefecture. The structure-activity relationship using various synthetic derivatives revealed the unique phenomenon that cell proliferation inhibitory activity of each enantiomer differs by 4 times. For expression of the cell proliferation inhibitory activity of bisacetylenic alcohols, "1-yn-3-ol" at both ends of the molecule is essential for the activity, and its cell growth inhibition mechanism is different from stabilization of the microtubule in the cytoplasm. The identification of the target molecule by immobilizing magnetic beads of bisacetylenic alcohol was planned. Currently, NHS-beads having "1-yn-3-ol" in one of the alkyl chain lengths 20 has been synthesized, and future target molecule will be identified using this molecular probe.