Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2-and VEGF(165)-mediated endothelial cell functions

Miller, Gavin J.; Hansen, Steen U.; Avizienyte, Egle; Rushton, Graham; Cole, Claire; Jayson, Gordon C.; Gardiner, John M.

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.

Citation

Miller, G. J., Hansen, S. U., Avizienyte, E., Rushton, G., Cole, C., Jayson, G. C., & Gardiner, J. M. (2013). Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2-and VEGF(165)-mediated endothelial cell functions. Chemical Science, 4(8), 3218 - 3222. https://doi.org/10.1039/C3SC51217G

• Journal Article Type: Article
• Acceptance Date: May 26, 2013
• Publication Date: May 28, 2013
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 8
• Pages: 3218 - 3222
• DOI: https://doi.org/10.1039/C3SC51217G
• Publisher URL: https://doi.org/10.1039/c3sc51217g