Advertisement

Multimeric peptides as agonists of the erythropoietin receptor

  • Oscar Vadas
  • Keith Rose
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

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 [1]. 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 [2]. In both cases, the avidity for EPOR and the biological activity tested...

Keywords

Cell Proliferation Assay Linker Length Succinic Anhydride Erythropoiesis Stimulate Agent Lysine Side Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was funded by the Swiss National Research Foundation (FNRS), the University of Geneva and the Schmidheiny Fondation.

References

  1. 1.
    Wrighton, N.C., et al. Science 273, 458–463 (1996).CrossRefGoogle Scholar
  2. 2.
    Johnson, D.L., et al. Chem Biol. 4, 939–950 (1997).CrossRefGoogle Scholar
  3. 3.
    Rose, K., et al. J. Am. Chem. Soc. 121, 7034–7038 (1999).CrossRefGoogle Scholar
  4. 4.
    Komatsu, N., et al. Blood 82, 456–464 (1993).Google Scholar
  5. 5.
    Mosmann, T. J. Immunol. Methods. 65, 55–63 (1983).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Oscar Vadas
    • 1
  • Keith Rose
    • 1
  1. 1.University Medical Center (CMU)Department of Structural Biology and BioinformaticsGeneva 4Switzerland.

Personalised recommendations