title: Sensitivity of opioid receptor binding to N-substituted maleimides and methanethiosulfonate derivatives.
abstract: A series of N-substituted maleimides was shown to effectively inactivate bremazocine binding to delta opioid receptors. Apparent second order rate constants for inactivation increased with increasing size of the N-substituent: N-methyl < N-ethyl < N-butyl < N-phenylmaleimide. It is suggested that the positive chain length effect is attributed to nonpolar interactions with the receptor in the vicinity of the reactive group. Binding to mu and delta opioid receptors was equally sensitive to inactivation by (2-aminoethyl)methanethiosulfonate; the [2-(trimethylammonium)ethyl] and (2-sulfonatoethyl) derivatives were less active. Site-directed mutagenesis of the mu opioid receptor indicated that Cys159, Cys190, Cys235, Cys292, or Cys321, residing in transmembrane domain 3, 4, 5, 6, and 7, respectively, were not the site of modification.
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Shahrestanifar
authors.forename: R D
authors.initials: RD
authors.lastname: Howells
mesh_terms: D001575:Benzomorphans / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D003545:Cysteine; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology*; D008698:Mesylates / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D001575:Benzomorphans; D008301:Maleimides; D008698:Mesylates; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D011994:Recombinant Proteins; C074502:methanethiosulfonate; C027248:bremazocine; D003545:Cysteine