Glycosyl-Enkephalins: Synthesis and Binding at the Mu, Delta & Kappa Opioid Receptors. Antinociception in Mice

  • Charles M. Keyari
  • Brian I. Knapp
  • Jean M. Bidlack
  • John Lowey
  • Edward J. Bilsky
  • Robin Polt
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Opioid peptides are unstable toward enzymatic biodegradation, resulting in poor bioavailability in tissues and organs, and hence are not effective analgesic agents. Glycosylation of small peptides increases the hydrophilicity, stability, and bioavailability of peptides and hence transport across the blood-brain barrier (BBB) [1, 2, 3]. BBB penetration studies of glycopeptides have indicated up to a 3-fold increase in the rate of brain delivery of these compounds compared with the unglycosylated parent peptides [4,5]. Also glycosylation of the naturally occurring μ-selective dermophin and δ-selective deltorphin opioid agonists resulted in analogues with higher brain permeability and greater analgesic actions [6,7]. Therefore, glycosylation seems to be an ideal strategy for the development of drug candidates for analgesia.

The carbohydrate moiety plays important roles in both the mechanism of transport of glycosylated peptides across the BBB, as well as stability towards...


Carbohydrate Moiety Kappa Opioid Receptor Automate Solid Phase Hydrophilic Side Chain MBHA Resin 
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.



We thank the Office of Naval Research (N00014-05-1-0807 & N00014-02-1-0471) and the National Science Foundation (CHE-607917) for support of these studies.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Charles M. Keyari
    • 1
  • Brian I. Knapp
    • 2
  • Jean M. Bidlack
    • 2
  • John Lowey
    • 3
  • Edward J. Bilsky
    • 3
  • Robin Polt
    • 1
  1. 1.Department of ChemistryThe University of ArizonaTucson AZ
  2. 2.University of New EnglandThe University of ArizonaTucson AZ
  3. 3.University of RochesterThe University of ArizonaTucson AZ

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