Oligosaccharides corresponding to the regular sequence of heparin: Chemical synthesis and interaction with FGF-2

It has been proposed that oligosaccharides corresponding to the so-called r egular region of heparin/heparan sulfate (HS) bind to fibroblast growth fac tor-2 (FGF-2). In order to explore the molecular basis of FGF/HS interactio n, we describe here the chemical synthesis of a tetra and a hexasaccharide, prepared as methyl glycosides, corresponding to the regular sequence of he parin. The strategy relies on the efficient preparation of three building b locks: a seeding block, an elongating block and a capping block. The hexasa ccharide inhibited the binding of FGF-2 on its receptor on human aorta vasc ular smooth muscle cells with an IC50 value (16 +/- 1.2 mu g/mL) close to t hat of standard heparin (14.8 +/- 0.5 mu g/mL) whereas the tetrasaccharide was much less potent (IC50 = 127 +/- 10.5 mu g/mL). The hexasaccharide and heparin, inhibited in a dose-dependent manner FGF-2 (30 nM) induced prolife ration (IC50 = 23.7 +/- 1.6 and 30.1 +/- 1.3 mu g/mL, respectively). Under the same experimental conditions, the tetrasaccharide only slightly inhibit ed the mitogenic effect of FGF-2 (IC50 > 100 mu g/mL). (C) 1999 Elsevier Sc ience Ltd. All rights reserved.