Conformational features responsible for the binding of cyclic analogues of enkephalin to opioid receptors

Models of μ- and δ-receptor-bound backbone conformations of enkephalin cyclic analogues containing Phe⁴ were determined by comparing geometrical similarity among the previously found low-energy, backbone structures of -enkephalinamide, -enkephalinamide, -enkephalin and -enkephalin. The present μ-receptor-bound conformation resembles a β-I bend in the peptide backbone centred on the Gly³-Phe⁴ region. Two slightly different models were found for the δ-receptor-bound conformation; both of them are more extended than the μ-receptor-bound conformation and include a γ-turn (or a γ-like turn) on the Gly³ residue. Energetically favourable rotamers of Tyr and Phc side chains were also determined for the μ- and δ-conformations. The present models of μ- and δ-conformations share geometrical similarity with the low-energy structures of Leu-enkephalin and the analogue.