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Rational Design of Peptidomimetics for Class B GPCRs: Potent Non-Peptide GLP-1 Receptor Agonists

  • Jung-Mo Ahn
  • Sun-Young Han
  • Eunice Murage
  • Martin Beinborn
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

The family of class B G-protein coupled receptors (GPCRs) includes cognate receptors for peptide hormones like secretin, glucagon, glucagon-like peptide-1 (GLP-1), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), pituitary adenylate cyclase activating peptide (PACAP), gastric inhibitory polypeptide (GIP), corticotropin-releasing factor (CRF), and so on. Whereas class A GPCRs recognize much smaller ligands, such as dopamine, somatostatin, and enkephalins, by mostly using residues in transmembrane domains and extracellular loops proximal to membrane, all class B GPCRs possess significantly long N-terminal chains and large extracellular loops which constitute multiple binding pockets to host their large ligands [1,2].

All of these class B peptides play unique and critical functions in human physiology and are found to be attractive to treat many diseases [2]. For instance, glucagon, GLP-1 and GIP are involved in glucose homeostasis and are potential novel...

Keywords

Vasoactive Intestinal Peptide Extracellular Loop Gastric Inhibitory Polypeptide Pituitary Adenylate Cyclase Activate Peptide Large Extracellular Loop 
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

The work was supported by Welch Foundation (AT-1595), American Diabetes Association (7-07-JF-02), and Texas Advanced Research Program (009741-0031-2006).

References

  1. 1.
    George, S. R., et al. Nature Rev. Drug Discovery 1, 808–820 (2002).CrossRefGoogle Scholar
  2. 2.
    Hoare, S. R. J. Drug Discovery Today 10, 417–427 (2005).CrossRefGoogle Scholar
  3. 3.
    Drucker, D. J. Diabetes Care 26, 2929–2940 (2003).CrossRefGoogle Scholar
  4. 4.
    Neer, R. M., et al. N. Engl. J. Med. 344, 1434–1441 (2001).CrossRefGoogle Scholar
  5. 5.
    Bale, T. L. and Vale, W. W. Annu. Rev. Pharmacol. Toxicol. 44, 525–557 (2004).CrossRefGoogle Scholar
  6. 6.
    Mesleh et al. J. Biol. Chem. 282, 6338–6346 (2007).CrossRefGoogle Scholar
  7. 7.
    Thornton, K. and Gorenstein, D. G. Biochemistry 33, 3532–3539 (1994).CrossRefGoogle Scholar
  8. 8.
    Tibaduiza, E. C., et al. J. Biol. Chem. 276, 37787–37793 (2001).Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jung-Mo Ahn
    • 1
  • Sun-Young Han
    • 1
  • Eunice Murage
    • 1
  • Martin Beinborn
    • 2
  1. 1.Department of ChemistryUniversity of Texas at DallasRichardsonUSA
  2. 2.Department of Medicine and Molecular Pharmacology Research CenterTupper Research Institute, New England Medical CenterBostonUSA

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