Electronic, Steric, and Hydrophobic Factors Influencing the Action of Enkephalin-Like Peptides on Opiate Receptors
- 1 January 1981
- journal article
- Published by Walter de Gruyter GmbH in Hoppe-Seyler´s Zeitschrift Für Physiologische Chemie
- Vol. 362 (1), 601-610
- https://doi.org/10.1515/bchm2.1981.362.1.601
Abstract
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.Keywords
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