Discovery of a TNF-alpha antagonist using chondroitin sulfate microarrays.
J Am Chem Soc
; 128(24): 7740-1, 2006 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-16771479
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfatos de Condroitina
/
Fator de Necrose Tumoral alfa
/
Apoptose
/
Análise Serial de Proteínas
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos