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J. Biol. Chem., Vol. 268, Issue 32, 23898-23905, Nov, 1993

Minimal sequence in heparin/heparan sulfate required for binding of basic fibroblast growth factor [published erratum appears in J Biol Chem 1994 Feb 4;269(5):3903]

M Maccarana, B Casu and U Lindahl
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.

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.
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