Imidazole dipeptides can quench toxic 4-oxo-2(E)-nonenal: Molecular mechanism and mass spectrometric characterization of the reaction products

Abstract

Imidazole dipeptides, such as carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-N^π -methyl-l-histidine), are highly localized in excitable tissues, including skeletal muscle and nervous tissue, and play important roles such as scavenging reactive oxygen species and quenching reactive aldehydes. We have demonstrated several reactions between imidazole dipeptides (namely, carnosine, and anserine) and a lipid peroxide-derived reactive aldehyde 4-oxo-2(E)-nonenal. Seven carnosine adducts and two anserine adducts were characterized using liquid chromatography/electrospray ionization-multiple-stage mass spectrometry. Adduct formation occurred between imidazole dipeptides and 4-oxo-2(E)-nonenal mainly through Michael addition, Schiff base formation, and/or Paal-Knorr reaction. The reactions were much more complicated than the reaction with a similar lipid peroxide-derived reactive aldehyde, 4-hydroxy-2(E)-nonenal.

Keywords: 4-oxo-2(E)-nonenal; Michael addition; Paal-Knorr reaction; Schiff base; anserine; carnosine; imidazole dipeptides.