Discovery of a TNF- Antagonist Using Chondroitin Sulfate Microarrays

J. Am. Chem. Soc., 128 (24), 7740 -7741, 2006. 10.1021/ja061906t S0002-7863(06)01906-8
Web Release Date: May 27, 2006

Discovery of a TNF- Antagonist Using Chondroitin Sulfate Microarrays

Sarah E. Tully, Manish Rawat, and Linda C. Hsieh-Wilson*

Division of Chemistry and Chemical Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125

lhw@caltech.edu

Received March 20, 2006

Abstract:

We report the first example of synthetic chondroitin sulfate (CS) microarrays to rapidly identify glycosaminoglycan-protein interactions and probe the specificity of proteins for distinct sulfation sequences. Using the microarrays, we identify a novel interaction between CS and TNF-, a proinflammatory cytokine involved in rheumatoid arthritis, Crohn's disease, and psoriasis. Moreover, we demonstrate that CS-E tetrasaccharides and polysaccharides enriched in the CS-E sulfation motif can inhibit the activity of this therapeutically important cytokine. We anticipate that carbohydrate microarrays will accelerate our understanding of glycosaminoglycan-protein interactions and the role of sulfation in modulating physiological and disease states.

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