title: Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.
abstract: To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Yangmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Margret
authors.initials: M
authors.lastname: Cazares
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Houghten
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Laurence
authors.initials: L
authors.lastname: Toll
authors.affiliation: Torrey Pines Institute for Molecular Studies , 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
authors.forename: Colette
authors.initials: C
authors.lastname: Dooley
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010456:Peptides, Cyclic; D017450:Receptors, Opioid, mu