Characterization of Adducts Formed in the Reactions of Methylglyoxal and Malonaldehyde with Lysine and Histidine Derivatives

Glycation of biopolymers by α‐oxoaldehydes such as methylglyoxal is believed to play a major role in the complex pathologies associated with diabetes and metabolic diseases. To design strategies that could interfere with the endogenous production of such aldehydes or promote their detoxification or, alternatively, to develop therapeutic procedures that could inhibit the deleterious effects of the oxoaldehydes at the cellular level, it is important to characterize the wide spectrum of reactions between these compounds and biomolecules, and gain insight into their mechanisms. In this study, we investigated the reactivity of endogenous α‐oxoaldehyde, methylglyoxal, and of malonaldehyde towards amino acid derivatives, and we identified new adducts with N^α‐acetyllysine and N^α‐acetylhistidine. In addition, we showed that a structurally analogous adduct is also formed with the model peptide N‐acetylglycyllysine O‐methyl ester. The characterized compounds were most likely derived from the addition of the appropriate nucleophilic center of the studied biomolecules to the C?C bond of the initially formed aldehyde conjugate. The resulted adducts contain an electrophilic β‐dicarbonyl moiety and could potentially be involved in the formation of DNA? protein or protein cross? links.