Synthesis and receptor binding affinity of both E‐and Z‐dehydro‐phenylaline4enkephalins*

The dehydrophenylalanine4‐enkephalin having the E‐configuration (ΔEPhe; phenyl and C = O,cis) was prepared by photoisomerization of the Z‐isomer with 3100 Å light, followed by reversed‐phase HPLC separation of the resulting mixture of the Z‐ and E‐isomers. In the radioligand receptor binding assays, the E‐isomer of [D‐Ala2, ΔPhe4, Leu5]enkephalin exhibited an extremely diminished affinity as compared with the Z‐isomer, namely 150–260‐fold loss of affinity for the delta and mu opiate receptors. The results indicate that the interrelationship of the Tyr1and Phe4residues in the enkephalin molecule seems to be of great importance in receptor recognition.