Arizona Health Sciences

Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors.

TitleVarious modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors.
Publication TypeJournal Article
Year of Publication2016
AuthorsLee YSun, Kupp R, Remesic MV, Ramos-Colon C, Hall SM, Chan C, Rankin D, Lai J, Porreca F, Hruby VJ
JournalChem Biol Drug Des
Volume88
Issue4
Pagination615-9
Date Published2016 Oct
ISSN1747-0285
KeywordsAnimals, Dynorphins, Inhibitory Concentration 50, Ligands, Rats, Receptors, Bradykinin, Structure-Activity Relationship
Abstract

As a unique endogenous opioid ligand, dynorphin A shows paradoxical neuroexcitatory effects at bradykinin receptors, and the effects are known to be amplified by the upregulation of dynorphin A under chronic pain and inflammatory conditions. In our earlier structure-activity relationship studies, the amphipathic dynorphin A fragment, [Des-Arg(7) ]-Dyn A-(4-11), was identified as a pharmacophore for the bradykinin receptors along with key structural features. Here, further modifications of the pharmacophore showed that the position of a Pro residue is also an important feature because of its role in making (or disrupting) a β-turn or 310 helix structure which is crucial for receptor recognition.

DOI10.1111/cbdd.12789
Alternate JournalChem Biol Drug Des
PubMed ID27203574
PubMed Central IDPMC5025351
Grant ListP01 DA006284 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Yeon Sun Lee
Frank Porreca, PhD