The interactions of glyoxals with proteins and DNA in relation to cancer

The interactions of glyoxal and methyl glyoxal with formamide, as a prototype of the peptide bond, and with DNA bases arc investigated using the cndo/2 method. For electron charge transfer to occur from the form-amide to the glyoxal, a stacked structure is needed. An unexpected planar hydrogen-bonded structure between the two molecules involving the regular hydrogen bond and a “pseudo hydrogen bond”, which involves the aldehydic proton of glyoxal and the oxygen atom of formamide, is found. Such a “hydrogen-bonded” arrangement is perfect geometrically for interaction with all four DNA bases. By exerting a competitive effect on base pairing between adenine and uracil (thymine), such interactions can account for the “brakelike” action of the glyoxals on cell proliferation, and hence cancerous growth, suggested by Szent-Györgyi.