Minimal sequence in heparin/heparan sulfate required for binding of basic fibroblast growth factor.
Experiments based on interaction in free solution between basic fibroblast growth factor (FGF-2) and saccharides related to heparin/heparan sulfate showed that the growth factor binds to heparin and to selectively glucosaminyl 6-O-desulfated heparin but poorly to iduronosyl 2-O-desulfated heparin. 2-O-sulfate groups thus are essential to the interaction, whereas 6-O-sulfates are not required nor do they interfere with FGF-2 binding. Comparison of various bound/nonbound oligosaccharides implicated a minimal pentasaccharide sequence for FGF-2 binding, with the structure: -hexuronic acid-glucosamine N-sulfate-hexuronic acid-glucosamine N-sulfate-iduronic acid 2-O-sulfate- (reducing terminus to the right). Such (overlapping) sequences are abundant in heparin, albeit heavily obscured by irrelevant O-sulfate groups, and occur also in heparan sulfate, with or without additional O-sulfates.
Maccarana
M
M
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
Casu
B
B
Lindahl
U
U
D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D013552:Swine
D016222:Fibroblast Growth Factor 2; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides