A dimeric peptide with erythropoiesis stimulating activity uniquely affects erythropoietin receptor ligation and cell surface expression
Abstract Erythropoiesis stimulating agents (ESAs) recently have been developed that exert long acting anti-anemia effects, but via poorly understood mechanisms. For one such ESA, peginesatide, analyses reveal unique EPOR binding properties for this synthetic EPOR agonist. As compared to rHu-EPO and...
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Published in | Experimental hematology Vol. 44; no. 8; pp. 765 - 769.e1 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Inc
01.08.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract Erythropoiesis stimulating agents (ESAs) recently have been developed that exert long acting anti-anemia effects, but via poorly understood mechanisms. For one such ESA, peginesatide, analyses reveal unique EPOR binding properties for this synthetic EPOR agonist. As compared to rHu-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 also unexpectedly up-modulated endogenous cell surface EPOR levels with parallel apparent relative 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 agonists. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0301-472X 1873-2399 |
DOI: | 10.1016/j.exphem.2016.04.015 |