99508-95-9

Upstream product

• 2065-75-0 2-Bromo-malonaldehyde 
• 961-07-9 2'-Deoxyguanosine 
• 108929-11-9 1,N²-etheno-2′-deoxyguanosine 
• 124762-93-2 2-Amino-1-methyl-4,5-dihydro-1H-imidazole-4,5-diol 

Downstream Products

• 961-07-9 2'-Deoxyguanosine 
• 124762-93-2 2-Amino-1-methyl-4,5-dihydro-1H-imidazole-4,5-diol 
• 104939-15-3 2-Amino-1-(2-hydroxy-3-methoxy-propyl)-4,5-dihydro-1H-imidazole-4,5-diol 

Relevant academic research and scientific papers

Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: A pathway to remove exocyclic DNA damage?

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-N2-etheno-2′-deoxyguanosine (1,N2-?dGuo) by singlet molecular oxygen (1O2) generated by a non-ionic water-soluble endoperoxide [N,N′-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide (DHPNO2)] and its corresponding oxygen isotopically labeled [18O]-[N,N′-di(2,3-dihydroxypropyl)-1,4- naphthalenedipropanamide endoperoxide (DHPN18O2)], 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 1O2 with the ?-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 1O2 by 1,N2-?dGuo and other etheno modified nucleosides. The rate constant (kt) values obtained for etheno nucleosides are comparable to the kt of dGuo. From these results, we suggest a possible role of 1O2 in the cleanup of etheno adducts by regenerating the normal base.

Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts.

Reactions of 9-ethylguanine, 2'-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by (1)H and (13)C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH 7. In addition to these, an N(2)-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N(2)-carboxymethyl-1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N(2)-ethenoguanine (5a-c) and N(2),3-ethenoguanine adducts (4a-c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N(2)-(1,2,2,3-tetrahydroxypropano)(8) and 1,N(2)-(2-formyl-1,2,3-trihydroxypropano)(9) adducts, was observed.