Potent agonists of a hematopoietic stem cell cytokine receptor, c-Mpl

Anna Tarasova, David Norman Haylock, Laurence Meagher, Cheang Ly Be, Jacinta White, Susan Kay Nilsson, Jessica Andrade, Kellie Cartledge, David Alan Winkler

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Several growth factors feature prominently in the control of hematopoiesis. Thrombopoietin, a class I hematopoietic cytokine, plays critical roles in regulating hematopoietic stem cell numbers and also stimulates the production and differentiation of megakaryocytes, the bone marrow cells that ultimately produce platelets. Thrombopoietin interacts with the c-Mpl cell-surface receptor. Recently, several peptide and small-molecule agonists and antagonists of c-Mpl have been reported. We conducted a bioinformatics and molecular modeling study aimed at understanding the agonist activities of peptides that bind to c-Mpl, and developed new potent peptide agonists with low nanomolar activity. These agonists also show very high activity in human CD34(+) primary cell cultures, and doubled the mean blood platelet counts when injected into mice.
Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalChemMedChem
Volume8
Issue number5
DOIs
Publication statusPublished - 2013

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