title: Discovery of dermorphin-based affinity labels with subnanomolar affinity for mu opioid receptors.
abstract: A series of potent electrophilic affinity labels (IC(50) = 0.1-5 nM) containing either a bromoacetamide or isothiocyanate based on the mu opioid receptor (MOR) selective peptide dermorphin were prepared. All four analogues exhibited wash resistant inhibition of [(3)H]DAMGO binding at subnanomolar to nanomolar concentrations, suggesting that these analogues bind covalently to MOR. To our knowledge, these peptides are the highest affinity peptide-based affinity labels for MOR reported to date.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Sinha
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Cao
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Murray
authors.forename: Jane V
authors.initials: JV
authors.lastname: Aldrich
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
chemical_list: D000345:Affinity Labels; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin