Design, synthesis, and binding characteristics of an opiate receptor mimetic peptide.

An artificial tetracontapeptide that mimicked the recognition/binding properties of naturally occurring opioid receptors was designed, synthesized, and purified to homogeneity. The design of the primary structure of the receptor mimetic peptide (RMP) accounted for secondary structure prediction rules and for the stereochemical anatomy of various enkephalin and morphine derivatives. The affinity of a series of opioid and nonopioid peptides to RMP was determined from their potency in displacing the binding of enzymatically prepared (14C)-[Leu]-enkephalin. The competition studies revealed that the binding is specific for endogenous opiate peptides, stereoselective for the naturally occurring L isomer of [Leu]-enkephalin, and discriminative for closely related opioid peptides. The thermodynamic parameters associated with the binding of [Leu]-enkephalin to RMP were evaluated from equilibrium studies at different temperatures. The van't Hoff plot of the resulting data was curvilinear. The formation of the ligand--RMP complex was characterized by a decrease both in entropy and in enthalpy with temperature. The thermodynamic behavior provided some evidence that hydrophobic interactions played a prominent role in stabilizing the [Leu]-enkephalin--RMP complex.