Journal of the American Chemical Society · 2006 · 226 citations · 4 references
Life SciencesBiochemistryMolecular BiologyGlycobiologyProteomicsSynthetic BiologyCarbohydrate RecognitionGlycan AnalysisGlycan RecognitionGlycan-protein InteractionsProtein GlycosylationProtein MicroarraysGlycan Array ScreeningGlycan MicroarraysHeparin-binding ProteinsHeparin-protein InteractionsHigh-throughput Screening AssaysOligosaccharide BindingOligosaccharide Library ConstructionOligosaccharide Synthesis
We present the first preparation of microarrays containing synthetic heparin oligosaccharides in order to elucidate the heparin-protein interactions involved in a variety of biological processes. For this purpose, we have developed a novel linker strategy that is compatible with the protecting-group manipulations required for the synthesis of the highly sulfated oligosaccharides and can also be extended to an automated solid phase approach. Strategic placement of the orthogonally protected amine linker was key to the success of the array construction. These heparin chips allow for the high-throughput screening of oligosaccharides by using approximately picomoles of protein. The potential of the new method was demonstrated by probing the carbohydrate affinity of two heparin-binding growth factors, FGF-1 and FGF-2, that are implicated in the development and differentiation of several tumors.
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