Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors

Yeon Sun Lee, Sara M. Hall, Cyf Ramos-Colon, Michael Remesic, Lindsay Lebaron, Ann Nguyen, David Rankin, Frank Porreca, Josephine Lai, Victor J. Hruby

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg7]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals. We have pursued further modification on the [des-Arg7]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.

Original languageEnglish (US)
Pages (from-to)30-33
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Amphipathicity
  • Anti-hyperalgesic effect
  • Bradykinin receptors
  • Dynorphin
  • Non-opioid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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