The reaction of 4-hydroxy-2-nonenal with N alpha-acetyl-L-histidine

The reaction of 4-hydroxy-2-nonenal and N alpha-acetyl-L-histidine was studied in pH 7.1 phosphate buffer. The main product isolated was assigned a cyclic hemiacetal structure formed by the addition of one of the imidazole nitrogen atoms to the alpha,beta-unsaturated aldehyde system of 4-hydroxy-2-nonenal. This structural assignment was based on the analyses of the NMR and mass spectral data of two derivatives obtained from the cyclic hemiacetal. The establishment of this cyclic hemiacetal structure supports the proposal made by Uchida and Stadtman6 that 4-hydroxy-2-nonenal modified histidyl residues in insulin by a Michael reaction.