Arizona Health Sciences

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

TitleModification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee YSun, Hall SM, Ramos-Colon C, Remesic M, LeBaron L, Nguyen A, Rankin D, Porreca F, Lai J, Hruby VJ
JournalBioorg Med Chem Lett
Volume25
Issue1
Pagination30-3
Date Published2015 Jan 01
ISSN1464-3405
KeywordsAnimals, Brain, Dynorphins, Rats, Receptors, Bradykinin, Structure-Activity Relationship
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-Arg(7)]-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-Arg(7)]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.

DOI10.1016/j.bmcl.2014.11.026
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID25434001
PubMed Central IDPMC4258438
Grant ListP01 DA006284 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
P01DA006284 / DA / NIDA NIH HHS / United States
R01DA013449 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Yeon Sun Lee
Frank Porreca, PhD