title: Structure-activity relationships of non-opioid [des-Arg(7)]-dynorphin A analogues for bradykinin receptors.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. Electronic address: yeon@email.arizona.edu.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rankin
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Cyf
authors.initials: C
authors.lastname: Ramos-Colon
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Jose Juan
authors.initials: JJ
authors.lastname: Ortiz
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kupp
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. Electronic address: hruby@email.arizona.edu.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004399:Dynorphins / Q000737:chemistry* / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D018002:Receptors, Bradykinin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018377:Neurotransmitter Agents; D018002:Receptors, Bradykinin; D004399:Dynorphins
keywords: Bradykinin receptors; Chronic pain; Non-opioid dynorphin A; Structure–activity relationship; pH sensitivity