Synthesis and biological activity of delta Phe4-enkephalins.

Abstract

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.

• Authors: Y Shimohigashi, C H Stammer, T Costa, P F Vonvoigtlander
• Journal: International journal of peptide and protein research (Int J Pept Protein Res) Vol. 22 Issue 4 Pg. 489-94 (Oct 1983) ISSN: 0367-8377 [Print] Denmark
• PMID: 6317582 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enkephalins
• Indicators and Reagents
• Receptors, Opioid
• Phenylalanine

Topics

• Analgesia
• Animals
• Biological Assay
• Brain (metabolism)
• Cell Membrane (metabolism)
• Enkephalins (chemical synthesis, metabolism, pharmacology)
• Indicators and Reagents
• Magnetic Resonance Spectroscopy
• Mice
• Phenylalanine
• Rats
• Receptors, Opioid (metabolism)
• Structure-Activity Relationship