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Peptide and Non-Peptide Mimetics Utilize Different Pathways for Signal Transduction

  • Victor J. Hruby
  • Minying Cai
  • Matt Dedek
  • Hongchang Qu
  • Erin Palmer
  • Alexander Mayorov
  • Dev. Trivedi
  • George Tsaprailis
  • Yingqui Yang
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Despite the central importance of peptides as drugs such as insulin, oxytocin, calcitonin, ace inhibitors, etc., there has been a prejudice against developing peptide drugs. Instead large efforts are made to develop non-peptide small molecules (“peptide mimetics”) to replace peptides. But are they true mimetics (same SAR, same bioactivity, same toxicity profile, etc.)? This issue generally has not been addressed directly. This is especially the case when the targets for the ligands are GPCRs. When the ligands are antagonists (for receptors, enzymes, etc.) this issue is not as critical as when the ligand is an agonist for a GPCR (or growth factors, or cytokines, etc.). The issue is highly relevant because biological function will depend on activation of a particular signaling pathway, and to obtain the same bioactivity will requirethe same SARs. To examine this conundrum we have begun to carefully evaluate whether peptide and non-peptide mimetics utilize the same...

Keywords

Delta Opioid Receptor Peptide Agonist Delta Opioid Biophysical Method Major Mutant 
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

Supported by grants from the U.S. Public Health Service, NIDDK and NIDA. We thank Prof. Robert Lefkowitz for the β-arrestin cDNA.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Victor J. Hruby
    • 1
    • 2
  • Minying Cai
    • 1
  • Matt Dedek
    • 1
  • Hongchang Qu
    • 1
  • Erin Palmer
    • 1
  • Alexander Mayorov
    • 1
  • Dev. Trivedi
    • 1
  • George Tsaprailis
    • 3
  • Yingqui Yang
    • 4
  1. 1.Department of ChemistryUniversity of ArizonaTucson
  2. 2.Department of PharmacologyUniversity of ArizonaTucson
  3. 3.Center for ToxicologyUniversity of ArizonaTucson
  4. 4.University of AlabamaBirmingham

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