Fibroblast growth factor 2, or FGF2, is a heparin-binding protein involved in a variety of biological functions such as angiogenesis, cellular migration and stem cell self renewal. Because of its ability to stimulate these cellular functions, FGF2 is useful for applications in wound healing and tissue regeneration. However, the ability to increase the activity of FGF2 and stabilize it to storage are critical for its clinical success. Heparin, a highly sulfated glycosaminoglycan is known to both stabilize FGF2 and is also required for protein binding to fibroblast growth factor receptors. In this talk, we will report a heparin-mimicking block copolymer that was designed to both stabilize FGF2 and facilitate binding with its receptors. The heparin-mimicking block copolymer was covalently conjugated to FGF2 through disulfide exchange between a pyridyl disulfide end group on the polymer and an exposed cysteine on the protein. The resulting conjugate remained active after storage at 4C and 23C for 7 days, whereas free FGF2 showed loss in activity. The conjugate was also tested for receptor binding abilities and showed increased receptor binding when compared to FGF2 alone in both a cell based assay and a receptor based enzyme-linked immunosorbant assay (ELISA). Furthermore, the conjugate was shown to stimulate endothelial cell migration and tubulogenesis statistically better than FGF2 in <i>in vitro</i> based assays. Together, these data suggest that the heparin-mimicking block copolymer conjugate could be useful in therapeutic applications to replace FGF2.

Synthesis of a superagonist heparin-mimicking block copolymer-FGF2 conjugate

253rd National Meeting (2017)

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