Kinetics amd mechanism of conformational changes of nucleic acids by interaction with small molecules

Research Project

Project/Area Number	25330338
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Life / Health / Medical informatics
Research Institution	Oita University
Principal Investigator	TANIGAWA Masato 大分大学, 医学部, 教授 (90332890)
Co-Investigator(Kenkyū-buntansha)	IWAKI Takafumi 大分大学, 医学部医学科, 助教 (60416419)
Co-Investigator(Renkei-kenkyūsha)	UEDA Kazuyoshi 横浜国立大学, 工学系研究院, 教授 (40223458)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2015: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000) Fiscal Year 2014: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000) Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords	生命分子計算 / DNA局所構造変化 / G-quadruplex / DNA / RNA / 円偏光二色性 / ストップトフロー / 分子動力学 / 分子動力学（MD） / 円偏光二色性（CD） / ストップトフロー（緩和時間） / ニコチンアミドモノヌクレオチド（NMN） / Idarubicin / irinotecan / ストップトフロー測定 / 対イオン / DNA凝集 / DNA間相互作用 / 熱安定性
Outline of Final Research Achievements	Oligonucletides with a G-rich sequence can form G-quadruplex. G-quadruplex exist in living cells and has drawn attention as a target for gene expression control, cell division, and design of drugs foe cancer. The binding of ligand TMPyP4 with G-quadruplex has been extensively studied. TMPyP4 is well known for the telomerase inhibiter, but interaction of the TMPyP4 and G-quadruplex were studied by ESI-MS, NMR, FRET, and circular dichroism. Irinotecan is a drug used for the treatment of cancer, and prevents DNA from unwinding by inhibition of topoisomerase. We make a hyposys that irinotecan is interact with G-quadruplex, because irinotecan resembles TMPyP4 in action mechanism. Stopped-flow circular dichroism is used to characterize the assembly of complexes consisting of G-quadruplex bound to the ligands. In this study, the rates of each process were determined over the temperature range of 10-50°C and activation energies were determined from the slope of Arrhenius plots.