Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation

Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturation at ambient temperatures and during long-time storage, which will reduce their biological activity. The interaction of FGFs with the sulfated domains of heparan sulfate and heparin is essential for their cellular signaling and stability. Therefore, we analyzed the interactions of FGF1 and FGF2 with four sulfated polysaccharides: heparin, dextran sulfate (DXS), lambda-carrageenan, and chondroitin sulfate. The results of thermal stability and cell proliferation assays demonstrate that heparin, DXS, and lambda-carrageenan bound to both FGFs and protected them from denaturation. Our results suggest heparin, DXS, and lambda-carrageenan are potential formulation materials that bind and stabilize FGFs, and which may also potentiate their activity and control their delivery.