Mechanism of formation of elastin crosslinks

We examined the formation of quaternary pyridinium crosslinks of elastin fo rmed by condensation of lysine and allysine residues using the model compou nds propanal (allysine) and n-butylamine (lysine) under quasi-physiological conditions. The resulting pyridinium compounds were characterized and the structure compared with the known pyridinium crosslinks, Three pyridinium c ompounds were identified and the structures were identical with the skeleto n of the crosslinking amino acids, desmosine (DES), isodesmosine (IDE), and pentasine, We concluded that a non-enzymatic pathway is available for the spontaneous generation of pyridinium crosslinks, To elucidate the intermedi ates and the mechanism of the formation of DES and IDE, we synthesized mode l intermediates from propanal and n-butylamine, and they were allowed to re act in three kinds of solvents, Then, the products were analyzed by an ion- pair reverse-phase HPLC. The results of this model system indicated that DE S and IDE can be formed by condensation of dehydromerodesmosine with dehydr olysinonorleucine and by condensation of allysine with dehydrolysinonorleuc ine, respectively, We also describe the mechanism of DES and IDE crosslinki ng.