Polypeptide-Polysaccharide Conjugates Produced by Spontaneous Non-Enzymatic Glycation1

A fundamental dogma has developed over the past 20 years that non-enzymatic glycation involving saccharide chains of greater than 3 to 4 residues is an extremely unlikely reaction. Our investigations using glycosaminoglycans have shown that, given sufficient time, polypeptide-polysaccharide conjugates form via the Schiff base-Amadori rearrangement mechanism. Further, even though these straight chain polysaccharides are relatively charged and sterically hindered, spontaneous glycation can also occur in vivo. A complete reinvestigation of all aldose terminating polysaccharides is required to elucidate this new class of macromolecules, which is likely to contain unusual polypeptide-polysaccharide combinations and functions.