MINIMAL SEQUENCE IN HEPARIN HEPARAN-SULFATE REQUIRED FOR BINDING OF BASIC FIBROBLAST GROWTH-FACTOR

Experiments based on interaction in free solution between basic fibrob last growth factor (FGF-2) and saccharides related to heparin/heparan sulfate showed that the growth factor binds to heparin and to selectiv ely glucosaminyl 6-O-desulfated heparin but poorly to iduronosyl 2-O-d esulfated heparin. 2-O-sulfate groups thus are essential to the intera ction, whereas 6-O-sulfates are not required nor do they interfere wit h 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-g lucosamine N-sulfate-iduronic acid 2-O-sulfate- (reducing terminus to the right). Such (overlapping) sequences are abundant in heparin, albe it heavily obscured by irrelevant O-sulfate groups, and occur also in heparan sulfate, with or without additional O-sulfates.