Ligand or GMP-140 selectin and methods of use thereof

Details Ligand or GMP-140 selectin and methods of use thereof Ligand or GMP-140 selectin and methods of use thereof

1995-06-06

1999-07-27

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 21, 514 23, 530395, 530396, 530402, 530403, C07K 100

Patent

active

059290366

ABSTRACT:
Fucosylated sialyated lactosaminoglycan structures that bind to GMP-140 have been discovered. The structure is created by expression of .alpha.(1,3) fucosyltransferases capable of modifying acceptors containing .alpha.(2,3) sialic acid-substituted lactosaminoglycans. Le.sup.x, Gal.beta.1,4(Fuc.alpha.1,3) GlcNAc.beta.1-R (where R is a protein or other carbohydrate structure), a common trisaccharide structure on myeloid cells but not on lymphocytes or erythroid cells, forms the core of this sialyated structure. The actual structure may be sialyl Le.sup.x, difucosyl sialyl Le.sup.x, a longer polyfucosylated polyactosaminoglycan, or a related variant. Several of these structures may bind to GMP-140 with various degrees of affinity. The carbohydrate structures, including sialyl Le.sup.x, difucosyl sialyl Le.sup.x, or a longer polyfucosylated polyactosaminoglycan variant, produced synthetically or expressed in genetically engineered cells, are useful as diagnostics and, in combination with a suitable pharmaceutical carrier, for clinical applications in the modulation or inhibition of coagulation processes or inflammatory processes. Antibodies to these structures can also be used as diagnostics and as pharmaceuticals for modulation of the coagulation or inflammatory processes.

REFERENCES:
Fukuda et al., "Structures of Sialylated Fucosyl Polylactosaminoglycans Isolated from CML Cells" J. Biol. Chem., v. 260, n. 24, pp. 12957-12967, (1985).
Moore et al., "Identification of Specific Glycoprotein Ligand for P-Selectin CD62 on Myeloid Cells", (1992) Biosis Abs #92:429190.
Gahmberg et al., "Major O-Glycosylated Sialoglycoproteins . . . " J. Cell. Biochem., (May 1988) 37 (1), 91-105.
Carlsson et al. "Structural Variations O-Linked Oligosaccharides . . . " J. Biol. Chem. (1986), 261(27), 12787-95.
Carlsson et al., "Isolation & Characterization Leukosialin . . . " J. Biol. Chem., (1986), 261(27), 12779-86.

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