Design of opioid peptides for a potential delta-receptor affinity label function: Comparison with the mu-specific Tyr-D-Ala-Gly-(Me)Phe-chloromethyl ketone

A. Z. Ronai, J. Hepp, A. Magyar, A. Borsodi, K. Medzihradszky

Research output: Article

5 Citations (Scopus)

Abstract

To find a δ-opioid receptor preferring peptide structure containing an Asp residue in a potentially interacting position, Tyr-Pro-Phe-Asp, Tyr-D-Ala-Phe-Asp, Tyr-D-Ala-Gly-Phe-Asp, Tyr-D-Ala-Gly-Phe-Asp α- and β-methyl ester and Tyr-Gly-Gly-Phe-Asp peptides were synthesized and their biological activities were analyzed in vitro in mouse vas deferens and longitudinal muscle strip of guinea pig ileum. Changing the β-methyl ester for an alkylating chloromethyl ketone moiety in the δ-receptor-selective agonist Tyr-D-Ala-Gly-Phe-Asp-β- methyl ester enhanced further the δ-receptor preference. The δ-receptor selective chloromethyl ketone but not the β-methyl ester gave a very slow washout after prolonged incubation in the mouse vas deferens bioassay; however, it was still readily displaceable by naloxone. The washout pattern of μ-specific Tyr-D-Ala-Gly-(Me)Phe chloromethyl ketone did not differ in the bioassays from that of the corresponding Gly5-ol derivative. Both chloromethyl ketones gave irreversible characteristics in the receptor binding assay.

Original languageEnglish
Pages (from-to)121-131
Number of pages11
JournalPharmacology
Volume49
Issue number2
DOIs
Publication statusPublished - jan. 1 1994

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Design of opioid peptides for a potential delta-receptor affinity label function: Comparison with the mu-specific Tyr-D-Ala-Gly-(Me)Phe-chloromethyl ketone'. Together they form a unique fingerprint.

  • Cite this