|Title||Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Lee YSun, Hall SM, Ramos-Colon C, Remesic M, LeBaron L, Nguyen A, Rankin D, Porreca F, Lai J, Hruby VJ|
|Journal||Bioorg Med Chem Lett|
|Date Published||2015 Jan 01|
|Keywords||Animals, Brain, Dynorphins, Rats, Receptors, Bradykinin, Structure-Activity Relationship|
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.
|Alternate Journal||Bioorg. Med. Chem. Lett.|
|PubMed Central ID||PMC4258438|
|Grant List||P01 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
Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors.
Faculty Member Reference:
Yeon Sun Lee, Ph.D.
Frank Porreca, Ph.D.