title: Oligosaccharides corresponding to the regular sequence of heparin: chemical synthesis and interaction with FGF-2.
abstract: It has been proposed that oligosaccharides corresponding to the so-called regular region of heparin/heparan sulfate (HS) bind to fibroblast growth factor-2 (FGF-2). In order to explore the molecular basis of FGF/HS interaction, we describe here the chemical synthesis of a tetra and a hexasaccharide, prepared as methyl glycosides, corresponding to the regular sequence of heparin. The strategy relies on the efficient preparation of three building blocks: a seeding block, an elongating block and a capping block. The hexasaccharide inhibited the binding of FGF-2 on its receptor on human aorta vascular smooth muscle cells with an IC50 value (16+/-1.2 microg/mL) close to that of standard heparin (14.8+/-0.5 microg/mL) whereas the tetrasaccharide was much less potent (IC50 = 127+/-10.5 microg/mL). The hexasaccharide and heparin, inhibited in a dose-dependent manner FGF-2 (30 nM) induced proliferation (IC50 = 23.7+/-1.6 and 30.1+/-1.3 microg/mL, respectively). Under the same experimental conditions, the tetrasaccharide only slightly inhibited the mitogenic effect of FGF-2 (IC50 > 100 microg/mL).
authors.affiliation: Ecole Normale Supérieure, Département de Chimie, Associé au CNRS, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tabeur
authors.forename: J M
authors.initials: JM
authors.lastname: Mallet
authors.forename: F
authors.initials: F
authors.lastname: Bono
authors.forename: J M
authors.initials: JM
authors.lastname: Herbert
authors.forename: M
authors.initials: M
authors.lastname: Petitou
authors.forename: P
authors.initials: P
authors.lastname: Sinaÿ
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002455:Cell Division; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay
chemical_list: D009844:Oligosaccharides; D016222:Fibroblast Growth Factor 2; D006493:Heparin