DISCOVERY OF A NOVEL THROMBOPOIETIN MIMIC AGONIST PEPTIDE

A random phage peptide library was constructed for the filamentous bac teriophage fuse5, The library was made by inserting a degenerate oligo nucleotide which encodes 15 variable amino acids into the NH2-terminal region of the phage gene III protein, This library, containing 1x10(9 ) different phages, was screened with a human immunoglobulin fusion pr otein containing the extracellular region of human thrombopoietin rece ptor, Several phages were isolated following four cycles of enrichment and amplification, These phages specifically bound to the fusion prot ein, One phage peptide acted as an agonist of the thrombopoietin recep tor, since it stimulated the proliferation of thrombopoietin-dependent cells and the differentiation of mouse bone marrow cells to megakaryo cytes. The amino acid sequence of this peptide is not present in the p rimary amino acid sequence of thrombopoietin, This discovery may lead to the design of a small-molecular mimic of thrombopoietin.