title: Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA. yeon@email.arizona.edu.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kupp
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Remesic
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Cyf
authors.initials: C
authors.lastname: Ramos-Colon
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rankin
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000737:chemistry* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008024:Ligands; D051381:Rats; D018002:Receptors, Bradykinin / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018002:Receptors, Bradykinin; D004399:Dynorphins
keywords: amphipathicity; bradykinin receptors; chronic pain; non-opioid dynorphin A; proline; structure-activity relationship