DNA Damage from Sulfite Autoxidation Catalyzed by a Nickel(II) Peptide

Abstract

Guanine-specific modification of both single- and double-stranded oligodeoxynucleotides via the autoxidation of sulfite is shown to be catalyzed by [NiCR]2+ (where CR = 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentaene) and [NiKGH-nh 2]+ (where KGH = lysylglycylhistidine). In the latter case, the nickel complex is proposed to act as a catalyst in three separate steps of sulfur oxide chemistry. Oxidative damage of guanines led to strand scission after piperidine treatment. The observed reactivity represents the first demonstration of DNA damage by sulfite and nickel(II) complexes. Importantly, these reactions were conducted using sulfite concentrations relevant to levels known to be cytotoxic. Mechanistic studies suggest the importance of both monoperoxysulfate and sulfate radical anion in the observed DNA damage. Evidence for formation of guanine radical cation as the initial product of DNA oxidation was found by comparison of the sequence dependence of guanine reactivity in a duplex restriction fragment. These studies underscore a role for sulfite in nickel toxicity and suggest a new method of site-specific oxidation with bioconjugates using sulfite rather than highly reactive oxidants such as monoperoxysulfate.

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

“…7 This selectivity of G oxidation in different sequence context has been also observed employing one-electron oxidants generated by photosensitization of metal complexes, 3,8 anthraquinones, 4,9 naphthalimides, 10 riboflavin (RF), 11,12 4′-pivaloyl derivatives, 13,14 cyanobenzoyl and cyanobenzophenone substituted 2′-deoxyuridine 15,16 and other chemical one-electron oxidants. 17, 18 Saito and co-workers have shown that the enhancement of oxidative guanine damage increases with the number of contiguous guanines according to 5′-G < 5′-GG < 5′-GGG and that this phenomenon is correlated with the calculated gas phase ionization potentials (IP) for guanines in different sequence contexts. 11,19,20 Siebbeles and co-workers calculated distributions of a positive charge in sequences of two or three adjacent guanines, flanked by other nucleobases that provide a useful model for mapping the reactivities of guanines in different sequence contexts.…”

Kinetics of the autoxidation of sulfur(iv) co-catalyzed by peroxodisulfate and silver(i) ions

“…2-5). The zeroth order nature of the predicted rate with respect to oxygen is easily seen from eqn (6).…”

“…[1][2][3][4][5] The role of sulfur(IV) autoxidation in the hydroxylation, epoxidation and oxidative cleavage of DNA, [6][7][8][9][10] in certain metallurgical 11,12 and food technologies, [13][14][15][16] and microbiological processes 17 generates additional motivation to study its mechanistic details. It is now understood that the process does not proceed in the absence of a catalyst in acidic medium.…”

Lesões em DNA induzidas pela autoxidação de S(IV) na presença de íons metálicos de transição

“…Experimentos realizados por Shi e Mao 48 mostram que a incubação de solução de sulfito com DNA por 4 h causa rendimento baixo de produção de lesão, no entanto, na presença de Cr(VI) são observados níveis maiores de quebra da dupla fita do DNA. Segundo esses autores, a oxidação de sulfito na presença de Cr(VI) gera somente o radical SO 3 •-, não sendo detectada a formação do radical •-(Equação 6) não é favorável (deduzido a partir dos potenciais de redução), havendo conseqüentemente a reação de dimerização do SO 5 •-para produzir SO 4 •-e O 2 (Equação 14) 8,9 . O radical SO 4 •-, que pode também ser formado como na Equação 9, possui um potencial de redução suficientemente alto (2,43 -3,08 V vs E.N.H.)…”

“…•'-) oxidam biomoléculas, incluindo lipídios, proteínas e DNA [7][8][9] . Alguns íons metálicos de transição têm um papel importante na formação desses radicais, uma vez que catalisam a oxidação de sulfito pelo oxigênio 10,11 .…”