Sulfation patterns of glycosaminoglycans encode molecular recognition and activity

被引:461
作者
Gama, Cristal I.
Tully, Sarah E.
Sotogaku, Naoki
Clark, Peter M.
Rawat, Manish
Vaidehi, Nagarajan
Goddard, William A., III
Nishi, Akinori
Hsieh-Wilson, Linda C. [1 ]
机构
[1] CALTECH, Dept Chem & Chem Engn, Pasadena, CA 91125 USA
[2] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA
[3] Kurume Univ, Sch Med, Dept Pharmacol, Kurume, Fukuoka 8300011, Japan
[4] CALTECH, Mat & Proc Simulat Ctr, Pasadena, CA 91125 USA
关键词
D O I
10.1038/nchembio810
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although glycosaminoglycans contribute to diverse physiological processes(1-4), 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.
引用
收藏
页码:467 / 473
页数:7
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