Abstract
A series of N-substituted maleimides was shown to effectively inactivate bremazocine binding to δ 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 μ and δ 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 μ opioid receptor indicated that Cys159, Cys190, Cys235, Cys292, or Cys321, residing in transmembrane domain 3, 4, 5, 6, and 7, respectively, werenot the site of modification.
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Special issue dedicated to Dr. Eric J. Simon.
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Shahrestanifar, M.S., Howells, R.D. Sensitivity of opioid receptor binding to N-substituted maleimides and methanethiosulfonate derivatives. Neurochem Res 21, 1295–1299 (1996). https://doi.org/10.1007/BF02532370
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DOI: https://doi.org/10.1007/BF02532370