Synthesis and biological activity of delta Phe4-enkephalins.
The delta Phe4-enkephalins have been synthesized and examined in an in vitro receptor binding assay and an in vivo tail flick analgesia test. The delta Phe4 residue was derived from Boc-Gly-Phe(beta-OH)-OH by spontaneous dehydration and azlactonization. The dipeptide azlactone was coupled directly with H-Leu-OBzl to yield a tripeptide which was converted into the pentapeptides after stepwise coupling with two amino acids using the water soluble EDC-HOBt method. Dehydroenkephalins were liberated with hydrogen fluoride in the presence of anisole. In the radioligand binding assay which did not contain an enzyme inhibitor [D-Ala2, delta Phe4, Leu5] enkephalin was almost twice as active as saturated [D-Ala2, D-Leu5]-enkephalin. The delta Phe4-enkephalins exhibited a considerably diminished activity as compared with the saturated peptide in the in vivo analgesic assay. These results are discussed with regard to the enzyme stability and receptor preference of dehydroenkephalins.
D000698:Analgesia; D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004745:Enkephalins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010649:Phenylalanine; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship
D004745:Enkephalins; D007202:Indicators and Reagents; D011957:Receptors, Opioid; D010649:Phenylalanine