Letter abstract
Nature Chemical Biology 2, 467 - 473 (2006)
Published online: 30 July 2006 | doi:10.1038/nchembio810
Sulfation patterns of glycosaminoglycans encode molecular recognition and activity
Cristal I Gama1,5, Sarah E Tully1,5, Naoki Sotogaku2, Peter M Clark1, Manish Rawat1, Nagarajan Vaidehi3,4, William A Goddard, III3, Akinori Nishi2 & Linda C Hsieh-Wilson1
Although glycosaminoglycans contribute to diverse physiological processes1, 2, 3, 4, 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.
- Division of Chemistry and Chemical Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
- Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
- Materials and Process Simulation Center (MSC), California Institute of Technology, Pasadena, California 91125, USA.
- Present address: Division of Immunology, City of Hope Cancer Research Center, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, California 91010, USA.
- These authors contributed equally to this work.
Correspondence to: Linda C Hsieh-Wilson1 e-mail: lhw@caltech.edu
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