The region in the μ opioid receptor conferring selectivity for sufentanil over the δ receptor is different from that over the κ receptor

AbstractWe determined the binding domains of sufentanil and lofentanil in the μ opioid receptor by comparing their binding affinities to seven μ/δ and six μ/κ chimeric receptors with those to μ, δ and κ opioid receptors. TMHs 6 and 7 and the e3 loop of the μ opioid receptor were important for selective binding of sufentanil and lofentanil to the μ over the κ receptor. TMHs 1–3 and the e1 loop of the μ opioid receptor conferred binding selectivity for sufentanil over the δ receptor. Thus, the region that conferred binding selectivity for sufentanil differs, depending on chimeras used. In addition, the interaction TMHs 1–3 and TMHs 6–7 was crucial for the high affinity binding of these two ligands. These two regions are likely to contain sites of interaction with the ligands or to confer conformations specific to the μ receptor