title: New NitroG-Grasp Molecules with Enhanced Capture Reactivity for 8-Nitroguanosine in the Aqueous Media.
abstract: 8-Nitroguanosine is formed by the nitration of guanosine, and has been conventionally classified as a genotoxic material. Recently, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has become of great interest due to its biological role as an intracellular signaling molecule. In an attempt to develop recognition molecules for 8-nitroguanosine, we have determined a 1,3-diazaphenoxazine nucleoside derivative (nitroG-grasp) bearing a thiol group with a urea linker, which efficiently displaces the nitro group through the formation of multiple hydrogen-bonded complexes with 8-nitroguanosine. However, a drawback of this capture molecule was that the displacement efficiency was not sufficient to capture 8-nitroguanosine in water. Taking into account that both the flexibility of the linker and the pKa value of the thiol group are determinants of the reactivity, new nitroG-grasp molecules were designed to have a fixed linker structure with different pKa values. Compared to the previous nitroG-grasp, the new compounds with the (2-aminophenyl)methanethiol or the propylene acetal of 3-amino-1-mercaptopropan-2-one unit have exhibited more than 10-100 times faster reactivity in the aqueous media. These compounds may be potential components to construct new nitroG-grasp molecules to capture 8-nitro-cGMP in the biological systems.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Fuchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000032:analysis; D008958:Models, Molecular; D009153:Mutagens / Q000032:analysis*; D009574:Nitro Compounds / Q000032:analysis*; D009705:Nucleosides / Q000737:chemistry*; D010078:Oxazines / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: C000601117:1,3-diazaphenoxazine; C481144:8-nitroguanosine; D001372:Aza Compounds; D009153:Mutagens; D009574:Nitro Compounds; D009705:Nucleosides; D010078:Oxazines; D013438:Sulfhydryl Compounds; D014867:Water; D006151:Guanosine; C005231:methylmercaptan