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Ago-Antagonists for G Protein-Coupled Peptide Hormone Receptor by Modifying the Agonist's Signalling Domain

  • Michael Beyermann
  • Nadja Heinrich
  • Klaus Fechner
  • Jens Furkert
  • Wei Zhang
  • Oliver Kraetke
  • Michael Bienert
  • Hartmut Berger
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Most of the pharmaceuticals today target at G protein-coupled receptors (GPCRs) [1] that transmit extracellular signals into cells. GPCRs are promiscuous, that means a single receptor can activate different signalling events, presumably via different G protein subtypes. Functional selectivity of GPCR ligands has been observed and points at a new orientation in pharmaceutical research. However, the structural characteristics of ligands that produce this selectivity are far from known [2].

The polypeptide hormone urocortin I (Ucn) activates both Gs and Gi proteins via the corticotropin-releasing factor receptor type 1 (CRF1). We have recently developed an easy method for the separate measurement of Gs and Gi activation at HEK 293 cells stably transfected with cDNA coding for CRF1 [3, 4]. The aim of this study was to search for structural determinants of the peptide agonist Ucn (DDPPLSIDLT FHLLRTLLEL ARTQSQRERA EQNRIIFDSV-NH2) that direct the signalling to Gs and Gi,...

Keywords

Single Receptor Peptide Agonist Stimulate cAMP Production Bulky Amino Acid Peptide Hormone Receptor 
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.

References

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    Davey, J. Expert Opinion on Therapeutic Targets 8, 165–170 (2004).CrossRefGoogle Scholar
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    Urban, J. D. et al. J. Pharmacol. Exp. Ther. 320, 1–13 (2007).CrossRefGoogle Scholar
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    Wietfeld, D. et al. J. Biol. Chem. 279, 38386–38394 (2004).CrossRefGoogle Scholar
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    Berger, H. et al. British J. Pharmacol. 149, 942–47 (2006).CrossRefGoogle Scholar
  5. 5.
    Beyermann, M. et al. British J Pharmacol., doi 10.1038 (2007).Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michael Beyermann
    • 1
  • Nadja Heinrich
    • 1
  • Klaus Fechner
    • 1
  • Jens Furkert
    • 1
  • Wei Zhang
    • 1
  • Oliver Kraetke
    • 1
  • Michael Bienert
    • 1
  • Hartmut Berger
    • 1
  1. 1.Department of Peptidchemistry/BiochemistryLeibniz-Institute of Molecular PharmacologyBerlin

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