Glycosaminoglycan-protein binding

GAGs exert their biological activities through interactions with proteins including growth factors and growth factor receptors. GAG structure vary according to spatial and temporal factors in tissue, giving rise to differential growth factor responses. We have used a combination of LC/MS profiling and tandem MS to query the HS or heparin oligosaccharide structures that bind to proteins of interest including antithrombin III and fibroblast growth factor 2. The results have demonstrated that abundant HS structures that bind proteins with relatively low affinity mask less abundant structure with significantly higher affinity. Work is continuing on both improvements of the GAG-protein binding analysis methods and on applications to growth factor binding questions.

  • Naimy, H.; Buczek-Thomas, J. A.; Nugent, M. A.; Leymarie, N.; Zaia, J. Highly sulfated non reducing end-derived heparan sulfate domains bind fibroblast growth factor-2 with high affinity and are enriched in biologically active fractions. J Biol Chem 2011, 286, 19311-19319. Pubmed Link
  • Naimy, H.; Leymarie, N.; Zaia, J. Screening for anticoagulant heparan sulfate octasaccharides and fine structure characterization using tandem mass spectrometry. Biochemistry 2010, 49, 3743-3752. Pubmed Link
  • Naimy, H.; Leymarie, N.; Bowman, M.; Zaia, J. Characterization of heparin oligosaccharides binding specifically to antithrombin III using mass spectrometry. Biochemistry 2008, 47, 3155-3161. Pubmed Link
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of BU School of Medicine