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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5319
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pubmed:dateCreated |
1997-6-30
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pubmed:abstractText |
Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14-amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant approximately 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC50 of 100 picomolar, which was equipotent to the 332-amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/MPL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thrombopoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombopoietin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0036-8075
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pubmed:author |
pubmed-author:BaccanariD PDP,
pubmed-author:BalasubramanianPP,
pubmed-author:BarrettR WRW,
pubmed-author:BoytosC MCM,
pubmed-author:CwirlaS ESE,
pubmed-author:DavisA MAM,
pubmed-author:DowerW JWJ,
pubmed-author:DuffinD JDJ,
pubmed-author:GatesC MCM,
pubmed-author:MattheakisL CLC,
pubmed-author:SchatzP JPJ,
pubmed-author:SingerS CSC,
pubmed-author:TansikR LRL,
pubmed-author:WagstromC RCR,
pubmed-author:WrightonN CNC
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1696-9
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pubmed:dateRevised |
2007-3-19
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pubmed:meshHeading |
pubmed-meshheading:9180079-Amino Acid Sequence,
pubmed-meshheading:9180079-Animals,
pubmed-meshheading:9180079-Binding, Competitive,
pubmed-meshheading:9180079-Blood Platelets,
pubmed-meshheading:9180079-Cell Division,
pubmed-meshheading:9180079-Cell Line,
pubmed-meshheading:9180079-Cells, Cultured,
pubmed-meshheading:9180079-Consensus Sequence,
pubmed-meshheading:9180079-Dimerization,
pubmed-meshheading:9180079-Erythropoietin,
pubmed-meshheading:9180079-Hematopoiesis,
pubmed-meshheading:9180079-Humans,
pubmed-meshheading:9180079-Megakaryocytes,
pubmed-meshheading:9180079-Mice,
pubmed-meshheading:9180079-Molecular Sequence Data,
pubmed-meshheading:9180079-Neoplasm Proteins,
pubmed-meshheading:9180079-Oligopeptides,
pubmed-meshheading:9180079-Peptide Library,
pubmed-meshheading:9180079-Peptides,
pubmed-meshheading:9180079-Platelet Count,
pubmed-meshheading:9180079-Proto-Oncogene Proteins,
pubmed-meshheading:9180079-Receptors, Cytokine,
pubmed-meshheading:9180079-Receptors, Thrombopoietin,
pubmed-meshheading:9180079-Recombinant Proteins,
pubmed-meshheading:9180079-Thrombopoietin,
pubmed-meshheading:9180079-Transfection
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pubmed:year |
1997
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pubmed:articleTitle |
Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine.
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pubmed:affiliation |
Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304, USA.
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pubmed:publicationType |
Journal Article
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