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Published June 21, 2006 | Supplemental Material
Journal Article Open

Discovery of a TNF-α Antagonist Using Chondroitin Sulfate Microarrays

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-α, 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.

Additional Information

© 2006 American Chemical Society. Received March 20, 2006. Publication Date (Web): May 27, 2006. We thank Dr. J. L. Riechmann, Director of the Millard and Muriel Jacobs Genetics and Genomics Laboratory at Caltech for assistance with printing the microarrays, and Dr. Susan Ou and Claude J. Rogers. This work was supported by the HFSP, NIH (RO1 NS045061, L.H.W.), NSF (S.E.T.), and HHMI.

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