Synthetic method for enhancing glycoprotein stability

Details Synthetic method for enhancing glycoprotein stability Synthetic method for enhancing glycoprotein stability

1991-11-04

1993-12-21

Naff, David M.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing compound containing saccharide radical

435 84, 435 85, 435 681, 435 6951, 435 76, C12P 1918, C12P 1926, C12P 1928, C12P 2100, C12P 2106, C12Q 100

Patent

active

052720667

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.fwdarw.galactose.fwdarw.N-acetylglucosamine.fwdarw.(SA.fwdarw.Gal.fwd arw.GlcNAc.fwdarw.), or tetrasaccharide (SA.fwdarw.Gal.fwdarw.GlcNAc.fwdarw.GlcNAc.fwdarw.) 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, GlcNAc, fucose or mannose residues. The method can also be used to mask antigenic determinants on foreign proteins which would otherwise pro

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