Chondroitin sulfate binding proteins and modulators thereof
Chondroitin sulfate polysaccharides with defined sulfation patterns can be synthesized. These chondroitin polysaccharides can be used to identify chondroitin sulfate binding proteins. Further, compounds that modulate the activity of chondroitin sulfate binding proteins can be identified. For example, TNF-α was found to bind specifically to CS-E and CS-E can be used to modulate the interaction of TNF-α with the TNF receptor.
1. A composition comprising homogeneous populations of chondroitin sulfate carbohydrates, wherein each homogeneous population of chondroitin sulfate carbohydrates is immobilized on an addressable location on a substrate, wherein each of said addressable locations is homogeneous for a particular chondroitin sulfate carbohydrate, wherein each of said addressable locations is separate from another addressable location, wherein said substrate comprises two or more addressable locations comprising chondroitin sulfate carbohydrates displaying different sulfation sequences, and wherein said chondroitin sulfate carbohydrates are selected from the group consisting of chondroitin sulfate A, chondroitin sulfate C, and chondroitin sulfate E.
2. The composition of claim 1 , wherein the substrate comprises a bead or a particle.
3. The composition of claim 2 , wherein the bead or particle comprises a paramagnetic bead or particle.
4. The composition of claim 2 , wherein the bead or particle comprises one or more of agarose, polystyrene, cellulose, cellulose acetate, carboxymethylcellulose, alginate, polyacrylamide, polyacrylate, polymethacrylic acid, polyvinylchloride, polytetrafluoroethylene, polyvinylacetate, silica, or glass.
5. The composition of claim 1 , wherein the substrate comprises a glass substrate.
6. A composition comprising one or more homogeneous populations of chondroitin sulfate carbohydrates, wherein each of the one or more homogeneous populations of chondroitin sulfate carbohydrates is immobilized on an addressable location on a substrate, wherein each of said addressable locations is homogeneous for a particular chondroitin sulfate carbohydrate, wherein said each of said addressable locations is separate from another addressable location of chondroitin sulfate carbohydrate on the substrate, and wherein the substrate comprises a poly-Lysine coated substrate.
7. The composition of claim 6 , wherein the poly-Lysine comprises poly-D-Lysine.
8. The composition of claim 6 , wherein the poly-Lysine comprises poly-L-Lysine.
9. The composition of claim 6 , wherein the CS molecules are non-covalently attached to a glass substrate.
10. The composition of claim 6 , wherein the CS molecules are covalently attached to the glass substrate.
11. The composition of claim 1 , wherein the CS is attached to the solid support in the form of an array.
12. The composition of claim 11 , wherein the chondroitin sulfate is selected from the group consisting of: a chondroitin sulfate A (CS-A) tetrasaccharide, a chondroitin sulfate C(CS-C) tetrasaccharide, a chondroitin sulfate E (CS-E) tetrasaccharide, a CS-A disaccharide, a CS-C disaccharide and a CS-E disaccharide.
13. The composition of claim 1 , wherein each population of chondroitin sulfate comprises a chondroitin sulfate selected from the group consisting of: a chondroitin sulfate A (CS-A) tetrasaccharide, a chondroitin sulfate C(CS-C) tetrasaccharide, a chondroitin sulfate E (CS-E) tetrasaccharide, a CS-A disaccharide, a CS-C disaccharide and a CS-E disaccharide.
14. The composition of claim 1 , wherein the CS polysaccharides are tetrasaccharides.
15. The composition of claim 1 , wherein the CS polysaccharides are disaccharides.
16. The composition of claim 1 , wherein said substrate is a poly-L-lysine coated glass substrate.