Ligands modified by circular permutation as agonists and antagonists
The present invention provides fusion polypeptides comprising polypeptide ligands that are modified by circular permutation and fused to at least one polypeptide fusion partner wherein such fusion polypeptides have new, improved or enhanced biological functions or activities. Such improvements include, but are not limited to, increased binding affinity, increased activity, increased agonist activity (super agonist), antagonist activity, increased accessibility, increased flexibility of the active site, increased stability, broader and/or changed substrate specificity, and combinations thereof.
1. A fusion polypeptide comprising the amino acids 1-303 of SEQ ID NO: 26 or an amino acid sequence homologous thereto having at least about 98% amino acid sequence identity over the length of amino acids 1-303 of SEQ ID NO: 26 and having the receptor agonist activity of amino acids 1-303 of SEQ ID NO: 26.
2. A pharmaceutical composition comprising the fusion polypeptide of claim 1 , and a pharmaceutically acceptable excipient.