Discovery of a novel thrombopoietin mimic agonist peptide.
A random phage peptide library was constructed for the filamentous bacteriophage fuse5. The library was made by inserting a degenerate oligonucleotide 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 protein containing the extracellular region of human thrombopoietin receptor. Several phages were isolated following four cycles of enrichment and amplification. These phages specifically bound to the fusion protein. One phage peptide acted as an agonist of the thrombopoietin receptor, since it stimulated the proliferation of thrombopoietin-dependent cells and the differentiation of mouse bone marrow cells to megakaryocytes. The amino acid sequence of this peptide is not present in the primary amino acid sequence of thrombopoietin. This discovery may lead to the design of a small-molecular mimic of thrombopoietin.
Kimura
T
T
Research and Development Division, Hokuriku Seiyaku Co., Ltd., Katsuyama, Fukui.
Kaburaki
H
H
Miyamoto
S
S
Katayama
J
J
Watanabe
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D017912:Inovirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009363:Neoplasm Proteins; D019151:Peptide Library; D010455:Peptides / Q000819:agonists* / Q000138:chemical synthesis / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D009363:Neoplasm Proteins; D019151:Peptide Library; D010455:Peptides; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin