Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with cysteine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with threonine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with valine and residue 134 is substituted cysteine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Abstract: The ?-trefoil protein human fibroblast growth factor-1 (FGF-1) is made up of a six-stranded anti-parallel ?-barrel closed off on one end by three ?-hairpins, thus exhibiting a three-fold axis of structural symmetry. The N- and C-termini ?-strands hydrogen bond to each other and are postulated from both NMR and X-ray structure data to represent a structurally-weakened region of the ?-barrel. Val mutations within the N- and C-termini ?-strands are shown to stabilize the structure and to increase van der Waals contacts by filling local cavities present within this region. Mutations that increase van der Waals contacts between both the N- and C-termini ?-strands are generally associated with significant reductions in the unfolding kinetics, and also increase the cooperativity of unfolding. Surprisingly, several mutant polypeptides herein disclosed greatly exceed the wild-type polypeptide in ability to stimulate human fibroblasts to proliferate.

Abstract: The ?-trefoil protein human fibroblast growth factor-1 (FGF-1) is made up of a six-stranded anti-parallel ?-barrel closed off on one end by three ?-hairpins, thus exhibiting a three-fold axis of structural symmetry. The N- and C-termini ?-strands hydrogen bond to each other and are postulated from both NMR and X-ray structure data to represent a structurally-weakened region of the ?-barrel. Val mutations within the N- and C-termini ?-strands are shown to stabilize the structure and to increase van der Waals contacts by filling local cavities present within this region. Mutations that increase van der Waals contacts between both the N- and C-termini ?-strands are generally associated with significant reductions in the unfolding kinetics, and also increase the cooperativity of unfolding. Surprisingly, several mutant polypeptides herein disclosed greatly exceed the wild-type polypeptide in ability to stimulate human fibroblasts to proliferate.

Abstract: Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residues 12 and 134 are substituted with cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenicity.