Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2- and VEGF165-mediated endothelial cell functions

Abstract

A concise chemical synthesis of a series of structurally-defined heparin-like oligosaccharides is described. This work provides an efficient entry to octa-, deca-, and dodecasaccharides, including the first synthesis of (GlcNS6S-IdoA2S)₅ and (GlcNS6S-IdoA2S)₆. Evaluation of the in vitro activity of these species against FGF2- and VEGF₁₆₅-dependent endothelial cell proliferation and migration establishes that octa- and decasaccharides are more potent in targeting FGF2-induced effects, where cell migration is affected more significantly than proliferation. These structure–activity relationships exemplify the significance of 6-O-sulfation in regulating the activity of angiogenic growth factors.