A dimeric peptide with erythropoiesis-stimulating activity uniquely affects erythropoietin receptor ligation and cell surface expression.

Document Type

Article

Publication Date

8-1-2016

Institution/Department

Maine Medical Center Research Institute

Journal Title

Experimental hematology

MeSH Headings

Cell Line, Cell Membrane, Erythropoiesis, Erythropoietin, Humans, Kinetics, Peptides, Protein Binding, Protein Multimerization, Receptors, Erythropoietin, Signal Transduction

Abstract

Erythropoiesis-stimulating agents (ESAs) that exert long-acting antianemia effects have been developed recently, but their mechanisms are poorly understood. Analyses reveal unique erythropoietin receptor (EPOR)-binding properties for one such ESA, the synthetic EPOR agonist peginesatide. Compared with recombinant human EPO and darbepoietin, peginesatide exhibited a slow on rate, but sustained EPOR residency and resistant displacement. In EPO-dependent human erythroid progenitor UT7epo cells, culture in peginesatide unexpectedly upmodulated endogenous cell surface EPOR levels with parallel increases in full-length EPOR-68K levels. These unique properties are suggested to contribute to the durable activity of this (and perhaps additional) dimeric peptide hematopoietic growth factor receptor agonist.

ISSN

1873-2399

First Page

765

Last Page

769

Link to Full Text

Share

COinS