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Discovery of a TNF-alpha antagonist using chondroitin sulfate microarrays. | LitMetric

Discovery of a TNF-alpha antagonist using chondroitin sulfate microarrays.

J Am Chem Soc

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

Published: June 2006

AI Article Synopsis

Article 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-alpha, 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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Source
http://dx.doi.org/10.1021/ja061906tDOI Listing

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