A synthetic heparan sulfate pentasaccharide, exclusively containing L-iduronic acid, displays higher affinity for FGF-2 than its D-glucuronic acid-containing isomers.
It has been suggested that the FGF-2 binding site on heparan sulfate chains is a trisulfated pentasaccharide containing three hexuronic acid units. The configuration at C-5 of two of them being undetermined, we have synthesized the four possible pentasaccharides, and have evaluated their FGF-2 binding affinity through in vitro biological assays. The pentasaccharide containing L-iduronic acid as the sole hexuronic acid showed higher affinity for FGF-2 than the other pentasaccharides, where one hexuronic acid unit at least is D-glucuronic acid.
Kovensky
J
J
Ecole Normale Supérieure, Département de Chimie, Associé au CNRS, Paris, France.
Duchaussoy
P
P
Bono
F
F
Salmivirta
M
M
Sizun
P
P
Herbert
J M
JM
Petitou
M
M
Sinaÿ
P
P
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry*; D006497:Heparan Sulfate / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007067:Iduronic Acid / Q000737:chemistry*; D007536:Isomerism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry
D016222:Fibroblast Growth Factor 2; D020723:Glucuronic Acid; D006497:Heparan Sulfate; D007067:Iduronic Acid; D009844:Oligosaccharides