On the Mechanism of Protein Crosslinking with Glutaraldehyde

Article abstract of DOI:10.1007/BF00904683

The interaction of glutaraldehyde with model aliphatic amines was studied in order to understand the crosslinking reaction of glutaraldehyde with proteins.The reaction in organic solvents gave N-alkyl-1,4-dihydropyridines and N,N'-dialkyl-1,5-diiminopentanes.The isolated products are new or were previously described by us for the first time.Hydration of the reaction products led to stable N-alkylpiperidines and N,N'-dialkyl-1,5-diaminopentanes.In aqueous solution the reaction dependens on the pH: at a pH above 7, N-alkyl-1,4-dihydropyridines and at a pH below 7, polym ers were obtained.For the crosslinking reaction of proteins with glutaraldehyde the following mechanism is proposed: Monomeric glutaraldehyde reacts with the protein to give intermediate N-alkyl-2,6-dihydroxypiperidines.Intramolecular dehydration leads to the corresponding N-alkyl-1,4-dihydropyridines.Condensation of the cyclic monohydrate of glutaraldehyde and N-alkyl-2,6-dihydroxypiperidines gives linear polymeric crosslinks containing α-oxo-N-alkylpiperidine units. - Keywords: Crosslinking mechanism; N-Alkyl-1,4-dihydropyridines; N,N'-Alkyl-1,5-diiminopentanes