New nitroG-grasp molecules with enhanced capture reactivity for 8-nitroguanosine in the aqueous media

Yasufumi Fuchi, Shigeki Sasaki

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume63
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

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