2013 Fiscal Year Final Research Report

Development of the selective capture molecule for 8-nitroguanosine

Research Project

Project/Area Number	24659008
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Single-year Grants
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)	2012-04-01 – 2014-03-31
Keywords	8-ニトログアノシン / 酸化損傷塩基 / 8-オキソグアノシン / 8-ﾆﾄﾛｸﾞｱﾉｼﾝﾓﾉﾘﾝﾘﾝ酸 / 検出
Research Abstract	In this study, we designed new thiol-containing recognition molecules for the covalent capture of 8-nitroguanosine based on the Gclamp skeleton by introducing thioalkylurea linker units of varying length (nitroG-grasp). The nitroG-grasp compound with C3 linker exhibited the most efficient guanylation even at low concentrations, supporting the selective complex formation for efficient reactivity for 8-nitro-G. The cyclen unit was attached to G-clamp molecule to recognize 8-oxoGTP, as a model compound of the cyclen-nitroG-grasp molecule. The Zn-complex of the cyclen-oxoG-clamp was able to discriminate 8-oxoGTP from GTP in aqueous media. The cyclen unit was also introduced to the nitroG-grasp molecule, which exhibited guanylation reaction for 8-nitroGMP without forming complex with zinc cation. In conclusion, this study has established the molecular basis for covalent capture of 8-nitroGTP and 8-nitroGMP.