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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Oxidation of 1-N-2-etheno-2'-deoxyguanosine by singlet molecular oxygen results in 2'-deoxyguanosine: a pathway to remove exocyclic DNA damage?

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Author(s):
Martinez, Glaucia Regina [1] ; Brum, Hulyana [1] ; Sassaki, Guilherme Lanzi [1] ; de Souza, Lauro Mera [2] ; de Melo Loureiro, Ana Paula [3] ; Gennari de Medeiros, Marisa Helena [4] ; Di Mascio, Paolo [4]
Total Authors: 7
Affiliation:
[1] UFPR, Setor Ciencias Biol, Dept Bioquim & Biol Mol, CP 19046, BR-81531980 Curitiba, PR - Brazil
[2] Fac Pequeno Principe, Inst Pesquisa Pele Pequeno Principe, Curitiba, PR - Brazil
[3] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, BR-05508000 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Inst Quim, Dept Bioquim, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Biological Chemistry; v. 399, n. 8, p. 859-867, AUG 2018.
Web of Science Citations: 0
Abstract

Exocyclic DNA adducts are considered as potential tools for the study of oxidative stress-related diseases, but an important aspect is their chemical reactivity towards oxidant species. We report here the oxidation of 1-N-2-etheno-2'-deoxyguanosine (1,N-2-epsilon dGuo) by singlet molecular oxygen (O-1(2)) generated by a non-ionic watersoluble endoperoxide {[}N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide (DHPNO2)] and its corresponding oxygen isotopically labeled {[}O-18]-{[}N,N'di( 2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide ((DHPNO)-O-18 (2))], and by photosensitization with two different photosensitizers {[}methylene blue (MB) and Rose Bengal (RB)]. Products detection and characterization were achieved using high performance liquid chromatography (HPLC) coupled to ultraviolet and electrospray ionization (ESI) tandem mass spectrometry, and nuclear magnetic resonance (NMR) analyses. We found that dGuo is regenerated via reaction of O-1(2) with the e-linkage, and we propose a dioxetane as an intermediate, which cleaves and loses the aldehyde groups as formate residues, or alternatively, it generates a 1,2-ethanediol adduct. We also report herein the quenching rate constants of O-1(2) by 1,N-2-epsilon dGuo and other etheno modified nucleosides. The rate constant (k(t)) values obtained for etheno nucleosides are comparable to the k(t) of dGuo. From these results, we suggest a possible role of O-1(2) in the cleanup of etheno adducts by regenerating the normal base. (AU)

FAPESP's process: 12/12663-1 - Singlet molecular oxygen and peroxides in chemical biology
Grantee:Paolo Di Mascio
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC