Synthetic heparan sulfate oligosaccharides inhibit endothelial cell functions essential for angiogenesis.

PloS One
Claire L ColeGordon C Jayson

Abstract

Heparan sulfate (HS) is an important regulator of the assembly and activity of various angiogenic signalling complexes. However, the significance of precisely defined HS structures in regulating cytokine-dependent angiogenic cellular functions and signalling through receptors regulating angiogenic responses remains unclear. Understanding such structure-activity relationships is important for the rational design of HS fragments that inhibit HS-dependent angiogenic signalling complexes. We synthesized a series of HS oligosaccharides ranging from 7 to 12 saccharide residues that contained a repeating disaccharide unit consisting of iduronate 2-O-sulfate linked to glucosamine with or without N-sulfate. The ability of oligosaccharides to compete with HS for FGF2 and VEGF165 binding significantly increased with oligosaccharide length and sulfation. Correspondingly, the inhibitory potential of oligosaccharides against FGF2- and VEGF165-induced endothelial cell responses was greater in longer oligosaccharide species that were comprised of disaccharides bearing both 2-O- and N-sulfation (2SNS). FGF2- and VEGF165-induced endothelial cell migration were inhibited by longer 2SNS oligosaccharide species with 2SNS dodecasaccharide activity b...Continue Reading

References

Dec 1, 1992·Glycobiology·J T Gallagher, J E Turnbull
Aug 26, 2000·Cytokine & Growth Factor Reviews·B BoillyX Le Bourhis
Feb 6, 2002·Chembiochem : a European Journal of Chemical Biology·J L de PazM Martín-Lomas
Jul 18, 2002·Nature Reviews. Drug Discovery·Rebecca Lever, Clive P Page
Sep 17, 2004·Journal of Cell Science·Cai HuangMichael D Schaller
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Satyajit K MitraDavid D Schlaepfer
May 3, 2005·Cytokine & Growth Factor Reviews·Moosa MohammadiOmar A Ibrahimi
Nov 1, 2005·The Journal of Biological Chemistry·Christopher J RobinsonSally E Stringer
Nov 22, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jurjees HasanGordon C Jayson
Mar 8, 2006·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Klas Norrby
May 20, 2006·Biochemical Society Transactions·B Mulloy, C C Rider
May 20, 2006·Biochemical Society Transactions·J T Gallagher
May 20, 2006·Biochemical Society Transactions·S E Stringer
Mar 31, 2007·Circulation Research·Laurent LamaliceJacques Huot
May 25, 2007·Nature Reviews. Molecular Cell Biology·Ralf H Adams, Kari Alitalo
Feb 19, 2008·The Journal of Biological Chemistry·Sarah J GoodgerJohn T Gallagher
Mar 20, 2009·Journal of Cell Science·Resham BhattacharyaDebabrata Mukhopadhyay
Sep 8, 2009·Nature Chemical Biology·Françoise BaleuxHugues Lortat-Jacob

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Citations

Jun 29, 2014·Glycobiology·Nadezhda E UstyuzhaninaNikolay E Nifantiev
Feb 19, 2013·Expert Review of Proteomics·Bernd GesslbauerAndreas J Kungl
Nov 18, 2014·Biochemical Society Transactions·Gordon C JaysonEgle Avizienyte
Sep 23, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Suwadee PhowichitSuvara K Wattanapitayakul
Mar 13, 2014·International Wound Journal·Shady HayekDenis Barritault
Mar 10, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Brooke L FarrugiaJohn M Whitelock
Apr 11, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marek BaráthJohn M Gardiner
Nov 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cinzia Lanzi, Giuliana Cassinelli
Aug 29, 2014·Cancer Research·Valeria SolariYves A DeClerck

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Methods Mentioned

BETA
column chromatography
size exclusion chromatography
NMR
ELISA
scraping
fluorescence microscopy
electrophoresis
glycosylation
FACS

Software Mentioned

FlowJo Analytical
GraphPad
GraphPad Prism
MetaMorph

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