GLYCATION DECREASES THE STABILITY OF THE TRIPLE-HELICAL STRANDS OF FIBROUS COLLAGEN AGAINST PROTEOLYTIC DEGRADATION BY PEPSIN IN A SPECIFICTEMPERATURE-RANGE

When fibrous collagen of rat tail tendons was glycated by incubation w ith ribose, it became highly insoluble in dilute acetic acid and resis tant to pepsin digestion at 5 degrees C, since it was cross-linked by advanced glycation end products, Extensively glycated fibrous collagen was found to be much less stable than non-glycated control fibrous co llagen against pepsin digestion at 30 degrees C, Under conditions wher e nearly all of the glycated fibrous collagen was degraded into small peptides by pepsin, approximately 45% of the control collagen was left as large polypeptides having nearly the whole length of its triple-he lical region, A soluble collagen, which consisted primarily of the tri ple-helical region of monomeric collagen, was found to be glycated as efficiently as the fibrous collagen on incubation with ribose at 30 de grees C, while the rate of cross-linking of the soluble collagen was v ery low, suggesting that the triple-helical strands do not undergo int ramolecular cross-linking and that most of the cross-links produced in the glycated fibrous collagen are intermolecular ones. The glycated s oluble collagen was as stable as the control collagen against pepsin d igestion at 30 degrees C, These results indicate that the triple-helic al strands of glycated fibrous collagen are much less stable than thos e of the non-glycated form against proteolytic digestion by pepsin at a temperature close to but below their melting point, Sugar-derived in termolecular crosslinks are supposed to underly the decreased stabilit y of the triple-helical strands.