Extended TIP(P) analogues as precursors for labeled δ-opioid receptor ligands

V. Kumar, Thomas F. Murray, J. V. Aldrich

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tyr-Tic-Phe-Phe-OH (TIPP) and the shorter Tyr-Tic-Phe-OH (TIP) peptides are potent and highly selective antagonists at the δ-opioid receptor and, therefore, are ideal candidates for the attachment of labels to assist in the study of δ-opioid receptors. Peptides extended at the C-terminus with residues which can be used as handles for further modification and/or labeling (i.e. Asx, Glx, and Lys) were synthesized. The TIPP-D/L-Asx/Glx derivatives exhibited similar δ-receptor affinity to TIPP (Ki = 5-10 nM vs Ki = 6 nM), and neither the location of the carboxylic acid moiety nor the stereochemistry of the C-terminal residue significantly affected the δ-receptor affinity of these derivatives. Extension of TIPP with an additional residue did not increase μ-receptor affinity, even though the position of the acidic group, which imparts δ-receptor selectivity to TIPP, was shifted relative to the carboxylic acid moiety of TIPP. The δ-receptor affinities of the TIP-D/L-Asx/Glx derivatives were found to be influenced mainly by the position of the carboxylic acid function rather than the stereochemistry of the C-terminal residue. TIP(P)-D/L-Lys(Ac)-OH derivatives exhibited, moderate δ-receptor affinity (Ki δ = 16-28 nM). The most potent compounds found in the extended TIP(P) series were TIPP-D-Gln-OH and TIP-D-Gln-OH (Ki δ = 5 nM) which had similar affinities to TIPP.

Original languageEnglish
Pages (from-to)5050-5054
Number of pages5
JournalJournal of Medicinal Chemistry
Volume43
Issue number26
DOIs
StatePublished - Dec 28 2000
Externally publishedYes

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Tics
Opioid Receptors
phenylalanylphenylalanine
Carboxylic Acids
Ligands
Derivatives
Stereochemistry
Peptides
Labeling
Labels
hydroxide ion
Narcotic Antagonists

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Extended TIP(P) analogues as precursors for labeled δ-opioid receptor ligands. / Kumar, V.; Murray, Thomas F.; Aldrich, J. V.

In: Journal of Medicinal Chemistry, Vol. 43, No. 26, 28.12.2000, p. 5050-5054.

Research output: Contribution to journalArticle

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