Heptapeptide Mimic of Ohmefentanyl Binding in the Discontinuous μ-Opiod Receptor^†

Ohmefentanyl binds to the rat μ-opiod receptor via two dipeptide sequences (Trp-His and Asp-Tyr) that are separated by 170 residues. A turn-inducing tripeptide, Pro-Aib-Aib, holds the dipeptides in a conformation that binds the narcotic (K_b = 7.1 × 10⁴ M^-1) in THF. Binding is specific for ohmefentanyl over morphine and is accompanied by a conformational change in the heptapeptide host. Control experiments with a Gly-Gly-Gly tripeptide linking the dipeptides show no evidence of binding.