Biomimicry is an important research tool, and since the 1990s, biomimicry has grown to be one of the major innovation tools for drug and therapeutic discoveries. Here, we describe the synthesis and application of a heparin-mimicking polymer, consisting of styrene sulfonate and poly(ethylene glycol) methyl ether methacrylate monomer units. This polymer stabilizes basic fibroblast growth factor (bFGF) upon covalent conjugation. bFGF is a protein that performs crucial roles in diverse cellular functions, such as angiogenesis, tissue and bone regeneration, stem cell self-renewal, and wound healing; however, its therapeutic usefulness is not yet exploited due to issues associated with stability during storage and delivery. The described bFGF-heparin-mimicking polymer conjugate retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors, such as heat, mild and harsh acidic conditions, prolonged storage and enzymatic degradation.  The native bFGF and control conjugate, where the styrene sulfonate monomer units were omitted from the polymer structure, were not stable to the same conditions. Furthermore, a second generation heparin-mimicking polymer has been identified that is capable of replacing heparin in facilitating binding of bFGF to its transmembrane tyrosine kinase receptors, which is the key event leading to cellular responses. These conjugate systems can be beneficial for the clinical use of bFGF and stabilization of heparin-binding growth factors in general.  Discovery and synthesis of the polymers, conjugates, biological activity, and medical applications will be discussed.

Heparin-mimicking polymer conjugates stabilize basic fibroblast growth factor

247th National Meeting (2014)

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