DNA–protein cross‐links are formed upon exposure to a variety of physical and exogenous, as well as endogenous chemical agents. This type of damage poses a threat to genomic integrity. Among the agents capable of inducing DNA–protein cross‐links bifunctional electrophiles arising from cellular processes deserve particular attention. Representatives of such electrophiles include glyoxal, methylglyoxal and malonaldehyde. Herein, we report that glyoxal and methylglyoxal adducts of 2′‐deoxyadenosine formed in the presence of malonaldehyde {M1Gx‐dA [8‐(diformylmethyl)‐3‐(2′‐deoxy‐β‐D‐ribofuranosyl)imidazo[2,1‐i]purine], and M1MGx‐dA [8‐(diformylmethyl)‐7‐methyl‐3‐(2′‐deoxy‐β‐D‐ribofuranosyl)imidazo[2,1‐i]purine], respectively}, display high reactivity towards lysine derivatives. In reactions with Nα‐acetyllysine M1Gx‐dA was found to form three adducts whereas M1MGx‐dA reacted with the lysine congener to form two stable products. All compounds were isolated and their structures determined on the basis of 2D NMR spectroscopy. Formation of the analogous products was shown in the individual reactions of M1Gx‐dA and M1MGx‐dA with Nϵ‐acetyllysine. Mechanisms proposed for formation of all characterised compounds are also discussed. This study reports identification of structures for a potentially new class of DNA–protein cross‐links.

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