Design of novel peptide ligands which have opioid agonist activity and CCK antagonist activity for the treatment of pain

Victor J Hruby, R. S. Agnes, P. Davis, S. W. Ma, Y. S. Lee, Todd W Vanderah, J. Lai, Frank Porreca

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Disease states such as neuropathic pain offer special challenges in drug design due to the system changes which accompany these diseases. In this manuscript we provide an example of a new approach to drug design in which we have modified a potent and selective peptide ligand for the CCK-2 receptor to a peptide which has potent agonist binding affinity and bioactivity at delta and mu opioid receptors, and simultaneous antagonist activity at CCK receptors. De novo design based on the concept of overlapping pharmacophores was a central hypothesis of this design, and led to compounds such as H-Tyr-DPhe-Gly-DTrp-NMeNle-Asp-Phe-NH2 (i.e., RSA 601) which have the designed properties.

Original languageEnglish (US)
Pages (from-to)699-704
Number of pages6
JournalLife Sciences
Volume73
Issue number6
DOIs
StatePublished - Jun 27 2003

Fingerprint

Cholecystokinin Receptors
Drug Design
Opioid Analgesics
Ligands
Pain
Peptides
delta Opioid Receptor
Narcotic Antagonists
mu Opioid Receptor
Neuralgia
Therapeutics
Bioactivity
Pharmaceutical Preparations
tyrosyl-phenylalanyl-glycyl-tryptophyl-N-methylnorleucyl-aspartyl-phenylalaninamide

Keywords

  • Cholecystokinin antagonists
  • Neuropathic pain
  • Opioid agonists
  • Peptide drug design

ASJC Scopus subject areas

  • Pharmacology

Cite this

Design of novel peptide ligands which have opioid agonist activity and CCK antagonist activity for the treatment of pain. / Hruby, Victor J; Agnes, R. S.; Davis, P.; Ma, S. W.; Lee, Y. S.; Vanderah, Todd W; Lai, J.; Porreca, Frank.

In: Life Sciences, Vol. 73, No. 6, 27.06.2003, p. 699-704.

Research output: Contribution to journalArticle

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