The ability of Fibroblast Growth Factor (FGF) to bind and dimerize with a receptor (FGFR) is mediated by heparin, a linear polysaccharide with primarily N-sulfated and 2-O and 6-O sulfated domains. To better understand the relationship between FGF:FGFR:polysaccharide interactions, we have developed a high-throughput platform that can be used to simultaneously screen a wide variety of variably sulfated polysaccharides for their ability to promote cellular activities. Highly sulfated polysaccharides (heparin and heparan sulfate) were compared against moderately sulfated polysaccharides (N-sulfo-heparosan), fully desulfated polysaccharides (N-acetyl-hepoarsan and an unmodified decasaccharide), and truncated ultra-low molecular weight heparins. Polysaccharides of varying length were prepared with site-specific N-, 2-O, and 6-O sulfations and screened for their biological activities. Additionally, low-molecular weight compounds were screened for their ability to interrupt FGF:FGFR:heparin complex formation and prevent cellular proliferation. The aforementioned polysaccharides were screened against multiple FGF-FGFR combinations and their effectiveness assessed via resulting cellular proliferation.

Screening fibroblast growth factor: Fibrobast growth factor receptor interactions with variable heparin-like polysaccharides

243rd National Meeting (2012)

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