Development of recognition molecules for 8-oxidized guanosine derivatives

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670004
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: Sasaki Shigeki 九州大学, 薬学研究科(研究院), 教授 (10170672)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ８－オキソグアノシン / ８－オキソグアノシントリリン酸 / ８－ニトログアノシン / ８－チオグアノシン / 共有結合的捕捉 / 認識分子 / 蛍光検出 / 酸化損傷塩基

Outline of Final Research Achievements

8-Oxidized guanosine derivatives such as 8-oxo-, 8-nitro-, 8-thio- or 8-halo-2’-deoxyguanosine are markers of redox stage of cells. In this study, we have attempted to develop new recognition molecules for these 8-oxidized guanosine derivatives. In an approach, silica gels were chemically modified with 8-oxo-G clamp and were shown to selectively detect 8-oxo-dG in water.Artificial receptor molecules for 8-oxo-dG triphosphate have been successfully developed by connecting the cyclen-zinc complex with the phenoxazine skeleton.In particular, the linker structure between the cyclen-zinc complex and the phenoxazine skeleton play an important role for selectivity for 8-oxo-dG triphosphate.Development of selective molecules for covalent capture of 8-nitro-2’-deoxyguanoine was also successful using the thiol-containing molecules named 8-nitroG grasp. The chloride leaving group was introduced to the same skeleton instead of the thiol group, and shown to covalently capture 8-thio-dG.

Free Research Field

化学系薬学