Reactions of nucleosides with glyoxal and acrolein

The structural determination of the products formed by the reaction of derivatives of glyoxal with guanine are reviewed, as are the applications of these reactions. Conditions have now been defined for the use of glyoxal as a probe for microdetermination of the structure of unidentified nucleic acid components. Unexpectedly, 3-methylguanine shows a positive reaction with glyoxal. The adduct produced has been isolated and characterized. A new ring is formed by substitution at the 1- and N2-positions of 3-methylguanine in this product. Acrolein reacts smoothly with 1-methylcytosine, cytidine and deoxycytidine at pH 4. The structures of the adducts have been determined. The amino group of cytosine adds to the double bond of acrolein, while the aldehyde binds to the 3-position, forming a new ring. Adenosine, deoxyadenosine and 9-methyladenine react in an analogous manner with acrolein, with ring formation involving the amino group and the N-1 of adenine. The orientation of addition is similar to that in the cytosine series. Guanosine reacts with excess acrolein at pH 4 to form a bis-adduct. Two new rings are fused to the guanine structure, one at N-1 and the amino group, and the other involving N-7 and C-8. A number of derivatives of this product have been obtained by glycosyl cleavage and imidazole-ring-opening reactions. However, the assignment of the orientation of addition for both acroleins remains tentative in this series.