Modified FGF-21 polypeptides with non-naturally encoded amino acids

A modified FGF-21 polypeptide comprising a non-naturally encoded amino acid,

• wherein said modified FGF-21 polypeptide maintains the biological activity of human FGF-21 and comprises a non-naturally encoded amino acid, and:
• (a) the modified FGF-21 polypeptide comprises a sequence at least 95% identical to SEQ ID NO:
• 1, SEQ ID NO:
• 2, SEQ ID NO:
• 3, SEQ ID NO:
• 4, SEQ ID NO:
• 5, SEQ ID NO:
• 6, or SEQ ID NO:
• 7;
• (b) the non-naturally encoded amino acid has the structure:
• wherein the R group is any substituent other than the side chain found in alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, pyrrolysine, or selenocysteine;
• (c) the modified FGF-21 polypeptide contains a substitution of an amino acid with the non-naturally encoded amino acid at a position in said modified FGF-21 polypeptide corresponding to residue 72, 77, 86, 108, 110, 131, or 146 of SEQ ID NO:
• 1;
• (d) the non-naturally encoded amino acid is linked to a linker or a polymer;
• and
• (e) the FGF-21 polypeptide has an in vivo half-life which is at least two-fold greater than the human FGF-21 polypeptide in SEQ ID NO:
• 1.