Multimeric peptides as agonists of the erythropoietin receptor
Erythropoietin (EPO) is a hormone that controls the proliferation and differentiation of red blood cells in bone marrow. The recombinant protein (rEPO) and other erythropoiesis stimulating agents are administered for the treatment of anaemia resulting from renal failure. EPO specifically interacts with EPO Receptor (EPOR) by inducing the reorientation of two receptor chains on the membrane, initiating signal transduction.
Small Erythropoietin Mimetic Peptides (EMP) that share no sequence similarities with the endogenous hormone were previously reported to activate EPOR . Crystal structure of EMP1 bound to EPOR demonstrated that two peptides were necessary to activate the dimeric receptor. Synthesis of EMP dimers to increase there biological activity by multivalency were synthesized, either with a commercial polyethylene glycol (PEG) as linker or using a C-terminal lysine residue as branchpoint . In both cases, the avidity for EPOR and the biological activity tested...
KeywordsCell Proliferation Assay Linker Length Succinic Anhydride Erythropoiesis Stimulate Agent Lysine Side Chain
This work was funded by the Swiss National Research Foundation (FNRS), the University of Geneva and the Schmidheiny Fondation.
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