|Title||Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Lee YSun, Kupp R, Remesic MV, Ramos-Colon C, Hall SM, Chan C, Rankin D, Lai J, Porreca F, Hruby VJ|
|Journal||Chem Biol Drug Des|
|Date Published||2016 Oct|
|Keywords||Animals, Dynorphins, Inhibitory Concentration 50, Ligands, Rats, Receptors, Bradykinin, Structure-Activity Relationship|
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.
|Alternate Journal||Chem Biol Drug Des|
|PubMed Central ID||PMC5025351|
|Grant List||P01 DA006284 / DA / NIDA NIH HHS / United States |
R01 DA013449 / DA / NIDA NIH HHS / United States
Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors.
Faculty Member Reference:
Yeon Sun Lee
Frank Porreca, PhD