Article: article from journal or magazin.
Electronic, steric, and hydrophobic factors influencing the action of enkephalin-like peptides on opiate receptors.
Hoppe-seyler's Zeitschrift Für Physiologische Chemie
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
The requirements of opiate receptors for electronic, steric, and hydrophobic properties of the amino acids in Pos. 4 and 5 of enkephalin-like peptides were studied. A series of [D-Ala2]-enkephalins containing carboranylalanine, adamantylalanine, t-butylglycine and p-nitrophenylalanine were synthesized and their pharmacological activities in the guinea pig ileum and their naloxone displacement in rat brain homogenates determined. An electronegative (-E) aromatic character of the amino acid in Pos. 4 strongly enhanced potency, overruling steric effects. The enhancement was not caused by exceptional enzyme resistance. Amino acid in Pos. 5 contributed to potency mainly through its effect on overall hydrophobicity. The two C-terminal amino acids seem to function as potentiator and address elements in the enkephalins.
Animals, Brain/metabolism, Endopeptidases, Endorphins/pharmacology, Enkephalins/pharmacology, Guinea Pigs, Ileum/drug effects, Naloxone/metabolism, Protein Conformation, Rats, Receptors, Opioid/metabolism, Structure-Activity Relationship
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