Heparin is a polysaccharide that is highly negatively charged due to numerous sulfate groups along the structure.  Heparin is an interesting target to mimic because it has a wide range of functions including blood anticoagulation, yet is heterogeneous and has batch-to-batch variability.  We developed a library of synthetic polymers that contain side chain sulfonate groups with the idea to develop a better-defined heparin-like molecule.  The library was screened for its ability to facilitate binding of fibroblast growth factor 2 (FGF2) to its receptors (FGFR) and thus mimic cell surface heparin sulfate (HS) proteoglycans.  The screening was undertaken with an engineered cell line that contains receptor but no HS proteoglycan, and the results were confirmed by an ELISA assay.  Poly(vinyl sulfonate) (pVS) was identified as the strongest FGFR activator, comparable to heparin.  This is significant because most heparin mimics have attenuated activity compared to heparin.  FGF2 elicits cell proliferation of fibroblast and endothelial cells, and HS proteoglycan are a low affinity receptor in this process.  Specifically, HS proteoglycans participate in the complexation of two FGF2 and two FGFRs, leading to signaling cascades.  The identified polymer and others were conjugated to FGF2.  The library screening and results of the FGF2 conjugates in cell proliferation, migration and angiogenesis assays will be presented.

Discovery and use of heparin mimetic polymers in angiogenesis

251st National Meeting (2016)

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