Development of new 1,3-diazaphenoxazine derivatives (thioG-grasp) to covalently capture 8-thioguanosine.

Yasufumi Fuchi,Hideto Obayashi,Shigeki Sasaki

doi:10.3390/molecules20011078

Abstract

The derivatives of 8-thioguanosine are thought to be included in the signal transduction system related to 8-nitroguanosine. In this study, we attempted to develop new 1,3-diazaphenoxazine (G-clamp) derivatives to covalently capture 8-thioguanosine (thioG-grasp). It was expected that the chlorine atom at the end of the linker would be displaced by the nucleophilic attack by the sulfur atom of 8-thioguanosine via multiple hydrogen-bonded complexes. The thioG-grasp derivative with a propyl linker reacted efficiently with 8-thioguanosine to form the corresponding adduct.

Highlights

Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS) are the chemical sources of oxidative stress, and they oxidize nucleic acids to produce the 8-oxoguanosine and 8-nitroguanosine derivatives [1,2,3]
We have focused on the development of recognition molecules for the 8-oxidized guanosine derivative based on the tricyclic cytosine analog “G-clamp” [8,9,10,11,12], and have reported the
We report the synthesis of 8-thioG-grasp derivatives and evaluated their reactivity with 8-thioguanosine

Summary

Introduction

Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS) are the chemical sources of oxidative stress, and they oxidize nucleic acids to produce the 8-oxoguanosine and 8-nitroguanosine derivatives [1,2,3]. Recent studies have revealed that nitrated-guanosine derivatives play important roles as signal messengers; 8-nitroguanosine-3′,5′-cyclic monophosphate (8-nitro-cGMP) is generated from guanosine- 5′-triphosphate (GTP) in response to the production of peroxynitrite (ONOO−) and reacts with the sulfhydryl groups of proteins [5], H2S/HS− [6] or persulfide [7] to form 8-adduct-cGMP (S-guanylation) or 8-thio-cGMP. These metabolic cycles have led to the proposal of a new signaling pathway mediated by 8-nitro-cGMP.

Methods

Results

Conclusion