Mechanism of formation of elastin crosslinks.
We examined the formation of quaternary pyridinium crosslinks of elastin formed by condensation of lysine and allysine residues using the model compounds 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 compounds were identified and the structures were identical with the skeleton 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 intermediates and the mechanism of the formation of DES and IDE, we synthesized model intermediates from propanal and n-butylamine, and they were allowed to react 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 DES and IDE can be formed by condensation of dehydromerodesmosine with dehydrolysinonorleucine and by condensation of allysine with dehydrolysinonorleucine, respectively. We also describe the mechanism of DES and IDE crosslinking.
Akagawa
M
M
Department of Applied Bioorganic Chemistry, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
Suyama
K
K
D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D002082:Butylamines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003432:Cross-Linking Reagents; D003895:Desmosine / Q000737:chemistry; D004549:Elastin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007524:Isodesmosine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry
D000447:Aldehydes; D000596:Amino Acids; D002082:Butylamines; D003432:Cross-Linking Reagents; D011726:Pyridinium Compounds; C052219:pentasine; D003895:Desmosine; D015074:2-Aminoadipic Acid; C000061:allysine; D004549:Elastin; D007524:Isodesmosine; C005556:propionaldehyde; D008239:Lysine; C032462:n-butylamine