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 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.

Optimizing Workflows for LC/MS Analysis of Co-Immunoprecipitated Protein Complexes – “Soap Opera (tions)”

“…One aim of the present editorial therefore is to suggest that the sequential use of OBG and PPS in LC-MS experiments should improve membrane protein extraction, better preserve co-IP complexes, lessen sample processing, improve LC-MS signals, and further extend insight into protein-protein partnerships. Direct testing of this suggested workflow is ongoing, including those involving EPO receptor associated interactions [26,27].…”