Modification of the Amino Group of Guanosine by Methylglyoxal and Other α-Ketoaldehydes in the Presence of Hydrogen Peroxide

Methylglyoxal is directly mutagenic to Salmonella typhimurium TA100 and its mutagenicity is markedly enhanced in the presence of hydrogen peroxide. We found that methylglyoxal in phosphate buffer was decomposed easily by hydrogen peroxide at room temperature to yield acetic acid and formic acid as major products and diacetyl as a minor product; acetyl radical was detected in the solution by ESR spectroscopy by the use of a spin-trapping reagent, 5, 5-dimethyl-1-pyrroline N-oxide. Furthermore, guanosine was coverted into N2-acetylguanosine by a combination of methylglyoxal and hydrogen peroxide in 0.1 M phosphate buffers (pH 6.1 to 7.4). This acetylation may be related to the enhancement of methylglyoxal mutagenicity by hydrogen peroxide. Other α-ketoaldehydes such as glyoxal and phenylglyoxal also yielded the corresponding acids and α-dicarbonyls upon reaction with hydrogen peroxide under the same conditions as above. These acids would have been produced through Baeyer-Villiger reaction or coupling of acyl radical with hydroxy radical, and dicarbonyls by dimerization of acyl radicals. In addition, when phenylglyoxal was used, the generation of benzoyl radial and the conversion of guanosine to N2-benzoylguanosine were observed. However, it remains to be established whether the generation of acyl radicals is directly involved in the N-2 acylation of guanosine.