Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins

BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER and Milos NOVOTNY. Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins. Chemical Research in Toxicology. Washington, DC (USA): American Chemical Society, 1998, vol. 11, No 7, p. 730-740. ISSN 08993228X.

Basic information

• Original name: Reaction of N-Acetylglycyllysine Methyl Ester with 2-Alkenals: An Alternative Model for Covalent Modification of Proteins
• Authors: BAKER, Andrew, Lukáš ŽÍDEK, Don WIESLER and Milos NOVOTNY.
• Edition: Chemical Research in Toxicology, Washington, DC (USA), American Chemical Society, 1998, 08993228X.

Other information

• Type of outcome: Article in a journal
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Faculty of Science
• Keywords in English: LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY; ADDUCTS; PEROXIDATION; ALDEHYDES; HISTIDINE; GLYCINE; LYSINE
• Tags: ADDUCTS, ALDEHYDES, GLYCINE, HISTIDINE, LOW-DENSITY-LIPOPROTEIN, LYSINE, MASS-SPECTROMETRY, PEROXIDATION

Abstract

Among the various reactions of lipid peroxidation products with proteins, 2-alkenals have been shown to react extensively with the epsilon-amino group of lysine residues [Zidek et al. (1997) Chem. Res. Toxicol. 10, 702-710]. To obtain additional information about the kinetic and mechanistic aspects of this modification, a model peptide (N-acetylglycyllysine O-methyl ester) was reacted with 2-hexenal. The reaction products were characterized through a combination of NMR and MS techniques. The structural elucidation efforts have shown the formation of pyridinium salts through the reaction of two or more alkenals with one amino group. Kinetic data were obtained using a continuous infusion of the reaction mixture into an electrospray ionization mass spectrometer. A mechanism is proposed that; offers an alternative model for the formation of stable protein cross-links. The reaction progresses through a Schiff base intermediate to form a dihydropyridine species which can be alternatively reduced to form various 3,4- or 2,5-substituted pyridinium species or react with another Schiff base to form a trialkyl-substituted pyridinium structure. The stoichiometry of this structure (aldehyde/amine) is 3:2, in contrast to the widely accepted 1:2. Therefore, it represents another possible crosslinking mechanism for bifunctional products of lipid peroxidation.