| abstract |
A method for modifying eukaryotic and prokaryotic proteins to extend their in vivo circulatory lifetimes. In the preferred embodiment, enzymatic and/or chemical treatments are used to produce a modified protein carrying one or more covalently attached trisaccharide, sialic acid→galactose→N-acetylglucosamine→(SA→Gal.fwdarw.GlcNac→), or tetrasaccharide (SA→Gal→GlcNAc→GlcNAc→) moieties. The method can be applied to any natural or recombinant protein possessing asparagine-linked oligosaccharides or to any non-glycosylated protein that can be chemically or enzymatically derivatized with the appropriate carbohydrate units. Following injection into an animal, the modified glycoproteins are protected from premature clearance by cells of the liver and reticulo-endothelial system which recognize and rapidly internalize circulating glycoproteins with carbohydrate chains containing terminal Gal, GlnNAc, fucose or mannose residues. The method can also be used to mask antigenic determinants on foreign proteins which would otherwise produce an immune response or to "target" a protein for recognition by sugar-specific cell surface receptors. |