Sulfation patterns of glycosaminoglycans encode molecular recognition and activity.
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.
Gama
Cristal I
CI
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Tully
Sarah E
SE
Sotogaku
Naoki
N
Clark
Peter M
PM
Rawat
Manish
M
Vaidehi
Nagarajan
N
Goddard
William A
WA
Nishi
Akinori
A
Hsieh-Wilson
Linda C
LC
D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D008958:Models, Molecular; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D006025:Glycosaminoglycans; D013431:Sulfates; D002809:Chondroitin Sulfates