title: Design, synthesis, and evaluation of new endomorphin analogs with enhanced central antinociception after peripheral administration.
abstract: We synthesized two novel endomorphin-1 (EM-1) analogs by substituting the C-terminus residue with (thienyl)-α-methylene-β-amino acids (Map). Several in vitro and in vivo assays were used to determine the activity of the analogs. The two EM-1 analogs showed subnanomolar binding affinity and functional activity at the μ-opioid receptor in HEK293 cells. Tail-flick and formalin tests further revealed that the EM-1 analogs were very effective after intravenous administration. Our results indicate that compared to endomorphin-1, the (thienyl)Map modified peptides showed improved blood-brain barrier permeability.
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mou
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of pharmacology, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, School of Life Science, Lanzhou University, Lanzhou 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1
keywords: Analgesia; Blood–brain barrier; Endomorphin; Unnatural amino acid