Synthesis, opiate receptor binding and analgesic activity of enkephalin analogues

Article abstract of DOI:10.1002/hlca.19790620206

The synthesis and biological testing of analogues of Met-enkephalin, a recently discovered opioid peptide from mammalian brain, are described. Testing involved determination of affinity constants for an opiate receptor site and of analgesic potency in the tail-flick test in mouse. The effects on opioid activity on modifying various parts of the enkephalin molecule are discussed. Tyr-D-Ala-Gly-MePhe-Met(O)-ol¹) (FK 33-824), which was highly active in these tests, was subsequently selected for clinical testing. The use of two complementary models - in vitro binding studies and in vivo test for analgesia - for the assessment of biological activity in the evaluation of analogues is explained.