Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1993-03-01
1997-07-22
Chan, Christina Y.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
435 2, A61K 3800, A61K 3512
Patent
active
056503890
ABSTRACT:
Decorin, a small collagen-binding dermatan sulfate proteoglycan, is widely distributed as a component of extracellular matrices. Using a solid phase binding assay, the inventors demonstrated that decorin bound C1q at physiologic pH and ionic strength. The interaction did not require divalent cations and was time and temperature dependent reaching equilibrium in 4 hours at 37.degree. C. Binding was specific and saturable with an apparent dissociation constant of 7.6.times.10.sup.-9 M. Decorin was shown to bind pepsin-derived fragments containing the collagenous domain of C1q and collagenase-derived fragments containing the globular domain of C1q. Since these fragments share a short sequence of amino acids, this finding suggests that decorin binds to a region of C1q located near the junction of the two domains. Competition studies using purified preparations of the decorin core protein and the glycosaminoglycan chains showed that only the former inhibited binding of decorin to C1q indicating that the interaction is mediated by the decorin core protein. Decorin was shown to inhibit the hemolytic activity of purified C1 as well as C1 in normal human serum. Approximately 50% inhibition was observed at a decorin concentration of 2 .mu.g/ml. Inhibition was not observed if C1 was bound to antigen-complexed antibody. Furthermore, neither the core protein, nor the glycosaminoglycan chain of decorin inhibited C1 indicating that the intact proteoglycan is necessary for functional activity. These studies therefore demonstrate the usefulness of decorin and related proteoglycans in suppression of complement activation of the immune system.
REFERENCES:
patent: 4990502 (1991-02-01), Cormeau et al.
patent: 5109114 (1992-04-01), Nicholson-Weller
patent: 5171674 (1992-12-01), Stevens et al.
Bidanset et al., "Binding of the Proteoglycan Dacorin to Collagen Type VI," The Journal of Biological Chemistry, 267 (8) :5250-5256, 1992.
Conrad et al.,"Antibodies Against the Predominant Glycosaminoglycan of the Mammalian Cornea, Keratan Sulfate-I," The Journal of Biological Chemistry, 257:464-471, 1982.
Cooper, Neil R., "The Classical Complement Pathway: Activation and Regulation of the First Complement Component," Advances in Immunology, 37:151-216, 1985.
Fisher et al., "Proteoglycans of Developing Bone," The Journal of Biological Chemistry, 258:6588-6594, 1983.
Funderburgh et al., "Arterial Lumican: Properties of a Corneal-Type Keratan Sulfate Proteoglycan from Bovine Aorta," The Journal of Biological Chemistry, 266:24773-24777, 1991.
Heinegard et al., "Two Novel Matrix Proteins Isolated from Articular Cartilage Show Wide Distributions among Connective Tissues," The Journal of Biological Chemistry, 261:13866-13872, 1986.
Krumdieck et al., "The Proteoglycan Decorin Binds Clq and Inhibits the Activity of the Cl Complex," The Journal of Immunology, 149(11):3695-3701, 1992.
Krumdieck et al., "Decorin Binds ClQ and Inhibits the Activity of Cl," FASEB Journal, 6(4):A1121, Abstract #1074, 1992.
Nakazawa et al., "Defective Processing of Keratan Sulfate in Macular Corneal Dystrophy," The Journal of Biological Chemistry, 259:13751-13757, 1994.
Quigg, R.J., "Inhibition of the Alternative Pathway of Complement by Glomerular Chondroitin Sulphate Proteoglycan," Immunology, 76:373-377, 1992.
Schumaker et al., "Activation of the First Componenet of Complement," Annual Reviews of Immunology, 5:21-42, 1987.
Vogel et al., "Specific Inhibition of Type I and Type II Collagen Fibrillogenesis by the Small Proteoglycan of Tendon," Biochemical Journal, 223:587-597, 1984.
Dialog Search Report dated Dec. 28, 1992 and Dec. 29, 1992.
Silvestry et al. J. Biol. Chem. 256: 7383-7387 (1981).
Scott Biochem. J. 252: 313-323 (1988).
Quigg Kidney Intl. 40: 668-676 (1991).
Quigg, R.J. (1991) "Isolation of a novel complement regulatory factor (GCRF) from glomerular epithelial cells", Kidney International, 40:668-676.
Scott, J. E. (1988) "Proteoglycan-fibrillar collagen interactions", Biochem. J., 252:313-323.
Silvestri, L. et al., (1981) "The Clq inhibitor in serum is a chondroitin 4-sulfate proteoglycan", J. Biol. Chem., 256:7383-7387.
PCT Search Report, mailed May 3, 1994.
Lizbfwski et al. in Paul, Raven Press 1993 Fundamental Immunology p. 932.
Almeda et al. J. Biol Chem. 258:785-791 (1983).
Morgan Eur. J. Clin Invest. 24:219-228 (1994).
Kalli et al. Springer Semin Immuno Pathol. 15:417-431 (1994).
Franklin Biochemical Pharmacology 49:267-273 (1995).
Hook Magnus A. O.
Krumdieck Richard
Volanakis John E.
Adler Benjamin Aaron
Chan Christina Y.
Gambel Phillip
University of Alabama at Birmingham Research Foundation
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