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. Rónai, J. Hepp, A. Magyar, A. Borsodi, K. Medzihradszky

Research output: Contribution to journalArticle

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
Publication statusPublished - 1994

Fingerprint

Affinity Labels
delta Opioid Receptor
Opioid Peptides
Ketones
Esters
Vas Deferens
Biological Assay
Peptides
Opioid Receptors
Naloxone
Ileum
Guinea Pigs
Muscles
tyrosyl-alanyl-glycyl-phenylalanine

Keywords

  • δ-receptor type
  • μ-receptor type
  • Chloromethyl ketone
  • Guinea pig ileum
  • Mouse vas deferens
  • Opioid receptor
  • Receptor binding assay

ASJC Scopus subject areas

  • Pharmacology

Cite this

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. / Rónai, A.; Hepp, J.; Magyar, A.; Borsodi, A.; Medzihradszky, K.

In: Pharmacology, Vol. 49, No. 2, 1994, p. 121-131.

Research output: Contribution to journalArticle

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