Modified Fibroblast Growth Factor 1 (FGF-1) Polypeptides with Increased Binding Affinity for Heparin and Associated Methods
A Mutant FGF-1 was designed so as to increase the intrinsic affinity for heparin sulfate glycosaminoglycan; involving a point mutation that introduces a basic amino acid (i.e. Arg or Lys) at position Ser116. Characterization of this mutant (S116R) shows reduction in mitogenic stimulation, increase in growth factor receptor-1c activation, and prolonged duration of glucose lowering in hyperglycemic mice. Such a mutant form can be advantageous in reducing blood glucose and as a novel insulin sensitizer to treat metabolic disorder.