δ and μ opiate receptor probes: fluorescent enkephalins with high receptor affinity and specificity

Abstract
The fluorescent amino acid, L‐1‐pyrenylalanine (Pya) was incorporated into [D‐Ala2,Leu5]enkephalin and its methyl ester at position 4 or 5. Pya‐enkephalins showed strong fluorescent intensity and displayed high binding affinity for opiate receptors. Pya4‐enkephalins showed high specificity for the μ receptors, while Pya5‐enkephalins showed high specificity and selectivity for the δ receptors. Particularly, [D‐Ala2,Pya5]enkephalin was as potent as the most utilized δ‐specific ligand of [D‐Ala2,D‐Leu5]enkephalin (DADLE), and yet its δ‐selectivity was about 5‐times greater than that of DADLE. Thus, Pya‐enkephalins per se can be utilized as a fluorescent probe or tracer for the opiate receptor‐binding assays.