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Show moreBackground of the invention: The present invention relates to a process for isolating and identifying a novel imidazo [4,5b] pyridinium molecule, referred to by the inventors as "pentosidine" from the extracellular matrix of humans and other mammals. The recently isolated imidazo [4,5b] pyridinium molecule, or pentosidine, is believed to be produced according to the non-enzymatic reaction of sugars with various amino acid or protein residues during the aging and/or degradation of proteins. In this regard, the pentosidine the molecule has been structurally characterized to consist essentially of a lysine and an arginine residue crosslinked by a pentose. Furthermore, the novel imidazo [4,5b] pyridinium or pentosidine molecule of the invention has been chemically synthesized in order to confirm the structural arrangement of the isolated molecule. The present invention is further directed to the use of the recently isolated, characterized, and chemically synthesized pentosidine molecule in various processes and/or compositions for studying the aging and/or degradation of proteins in humans and other mammals. The extracellular matrix of humans and other mammals undergoes progressive changes during aging that are characterized by decreased solubility (Schnider, S. L., and Kohn, R. R., J. Clin. Invest. 67, pp. 1630-1635, 1981), decreased proteolytic digestibility (Hamlin, C. R., Luschin, J. H., and Kohn, R. R., Exp. Gerontol. 13, pp. 415-523, 1978), increased heat denaturation time (Snowden, J. M., Eyre, D. R., and Swann, D. H., Biochem. Biophys. Acta, 706, pp. 153-157, 1982) and accumulation of yellow and fluorescent material (LaBella, F. S., and Paul, G., J. Gerontol., 20, pp. 54-59, 1964). These changes, which affect particularly collagen-rich tissues and appear to be accelerated in diabetes, are thought to result from the formation of age-related intermolecular crosslinks. Elucidation of the structure of these age-related intermolecular crosslinks has been for many years of major interest to gerontologists and collagen chemists for two principal reasons. First, there appears to exist an inverse relationship between mammalian longevity and aging rate of collagen (Kohn, R. R. in Testing the Theories of Aging (Adelman, R. C., and Roth, G. S., eds.) pp. 221-231, CRC Press, Inc., Boca Raton, Fla.) suggesting that the process which governs longevity may express itself at least partially in the aging rate of collagen. Second, the progressive increase in stiffness of collagen-rich tissues like arteries, lungs, joints and the extracellular matrix has been associated with age-related diseases such as hypertension, emphysema, decreased joint mobility and ability to fight infections. Thus, elucidation of the nature of extracellular matrix crosslinking in aging is of both practical and theoretical interest.
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