Arizona Health Sciences

Structure-activity relationships of non-opioid [des-Arg(7)]-dynorphin A analogues for bradykinin receptors.

TitleStructure-activity relationships of non-opioid [des-Arg(7)]-dynorphin A analogues for bradykinin receptors.
Publication TypeJournal Article
Year of Publication2014
AuthorsLee YSun, Rankin D, Hall SM, Ramos-Colon C, Ortiz JJuan, Kupp R, Porreca F, Lai J, Hruby VJ
JournalBioorg Med Chem Lett
Volume24
Issue21
Pagination4976-9
Date Published2014 Nov 01
ISSN1464-3405
KeywordsAnimals, Brain, Dynorphins, Neurotransmitter Agents, Rats, Receptors, Bradykinin, Structure-Activity Relationship
Abstract

In our earlier studies, bradykinin receptors (BRs) were identified as a potential target for the neuroexcitatory effects of dynorphin A (Dyn A) in the central nervous system (CNS), and [des-Arg(7)]-Dyn A-(4-11) (6) was discovered as a lead ligand to modulate Dyn A-(2-13) induced neuroexcitatory effects in the CNS as an antagonist. In an effort to gain insights into key structural features of the Dyn A for the BRs, we pursued further structure-activity relationships (SAR) study on the [des-Arg(7)]-Dyn A analogs and confirmed that all of the [des-Arg(7)]-Dyn A analogues showed good binding affinities at the BRs.

DOI10.1016/j.bmcl.2014.09.033
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID25282551
PubMed Central IDPMC4250343
Grant ListP01 DA006284 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
NIDA P01DA006284 / / PHS HHS / United States
R01DA013449 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Yeon Sun Lee, Ph.D.
Frank Porreca, PhD