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Application of Highly Potent and Ultraselective delta Opioidmimetic Peptide Antagonists for Biochemical, Pharmacological, Clinic

Posted Jun 14 2010 5:00pm

Description of Invention:
The National Institute of Environmental Health Sciences has determined the specific chemical structure, high potency and selectivity of a series of unique opioid di- and tripeptide antagonists. The most active dipeptide exhibited an affinity for the delta opioid receptor of 0.022 nM and a delta selectivity of 150,000 (relative to the µ receptor); affinity toward kappa receptors was negligible (> 20 µM). The tripeptide had delta selectivity of 20,000 and was similarly without effect on kappa receptors (> 50 µM). Pharmacological functional bioassays in vitro indicated antagonistic activity at delta receptors without activity toward µ receptors (> 10 µM), which makes these compounds more utilitarian than the commonly employed delta antagonist naltrindole. Similarly, in vivo data in mice confirmed the antagonistic behavior of these peptides. Furthermore, the molecular model of the low energy conformer indicated a unique solution topography of a universal antagonist.

  • The preparation of radiolabelled ligands for the biochemical characterization of the delta opioid receptor, localization of this receptor in animal tissues by various immunohistochemical methods, and body distribution/ compartmentalization kinetics, such as in determining the extent of transit across the blood-brain barrier. Current radioactive opioid ligands generally have lower affinities and are considerably less selective by orders of magnitude than our opioid dipeptide.
  • The preparation of large quantities of highly pure peptide for pharmacological and physiological studies in the laboratory, and their availability for animal and clinical trials, and eventually for therapeutic applications in medical orientated facilities. For example, the potential for treatment of alcohol dependency and narcotic addiction, obesity, and suppression of the immune response in organ transplants, in addition to other numerous clinical situations. These proposed studies would eventually necessitate multigram quantities of the dipeptide in spite of its high affinity and selectivity.
  • Production of monoclonal antibodies to these peptides would provide science with high affinity substances that could be effectively used in both the laboratory and clinical settings.

Lawrence H Lazarus (NIEHS)

Patent Status:
HHS, Reference No. E-171-1994/0
US, , Patent No. 5,780,589, Issued 14 Jul 1998
HHS, Reference No. E-171-1994/0
PCT, Application No. PCT/US95/15510 filed 30 Nov 1995

Central Nervous System
Central Nervous System - Therapeutics
Central Nervous System - Research Materials
In-vivo Data
In-vitro Data

For Additional Information Please Contact:
Steven Standley Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-4074
Fax: 301-402-0220

Ref No: 260

Updated: 06/2010

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