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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
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]
Número total de Autores: 7
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Biological Chemistry; v. 399, n. 8, p. 859-867, AUG 2018.
Citações Web of Science: 0

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)

Processo FAPESP: 12/12663-1 - Oxigênio singlete e peróxidos em química biológica
Beneficiário:Paolo Di Mascio
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs