title: Partial retro-inverso, retro, and inverso modifications of hydrazide linked bifunctional peptides for opioid and cholecystokinin (CCK) receptors.
abstract: Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the delta and mu opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Richard S
authors.initials: RS
authors.lastname: Agnes
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Shou-wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Hamid
authors.initials: H
authors.lastname: Badghisi
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu