Sulfation patterns of glycosaminoglycans encode molecular recognition and activity

Cristal I. Gama, Sarah E. Tully, Naoki Sotogaku, Peter M. Clark, Manish Rawat, Nagarajan Vaidehi, William A. Goddard, Akinori Nishi, Linda C. Hsieh-Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Although glycosaminoglycans contribute to diverse physiological processes, an understanding of their molecular mechanisms has been hampered by the inability to access homogeneous glycosaminoglycan structures. Here, we assembled well-defined chondroitin sulfate oligosaccharides using a convergent, synthetic approach that permits installation of sulfate groups at precise positions along the carbohydrate backbone. Using these defined structures, we demonstrate that specific sulfation motifs function as molecular recognition elements for growth factors and modulate neuronal growth. These results provide both fundamental insights into the role of sulfation and direct evidence for a 'sulfation code' whereby glycosaminoglycans encode functional information in a sequence-specific manner analogous to that of DNA, RNA and proteins.

Original languageEnglish
Pages (from-to)467-473
Number of pages7
JournalNature Chemical Biology
Volume2
Issue number9
DOIs
Publication statusPublished - 1 Jan 2006
Externally publishedYes

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