(4-Carboxamido)phenylalanine is a surrogate for tyrosine in opioid receptor peptide ligands

Roland E. Dolle, Mathieu Machaut, Blanca Martinez-Teipel, Serge Belanger, Joel A. Cassel, Gabriel J. Stabley, Thomas M. Graczyk, Robert N. DeHaven

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

(S)-4-(Carboxamido)phenylalanine (Cpa) is examined as a bioisosteric replacement for the terminal tyrosine (Tyr) residue in a variety of known peptide ligands for the μ, δ, and κ opioid receptors. The Cpa-containing peptides, assayed against cloned human opioid receptors, display comparable binding affinity (Ki), and agonist potency (EC 50) to the parent ligands at the three receptors. Cpa analogs of δ selective peptides show an increase in δ selectivity relative to the μ receptor. Cpa is the first example of an amino acid that acts as a surrogate for Tyr in opioid peptide ligands, challenging the long-standing belief that a phenolic residue is required for high affinity binding.

Original languageEnglish
Pages (from-to)3545-3548
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number13
DOIs
StatePublished - Jul 5 2004
Externally publishedYes

Keywords

  • Opioid peptide

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    Dolle, R. E., Machaut, M., Martinez-Teipel, B., Belanger, S., Cassel, J. A., Stabley, G. J., Graczyk, T. M., & DeHaven, R. N. (2004). (4-Carboxamido)phenylalanine is a surrogate for tyrosine in opioid receptor peptide ligands. Bioorganic and Medicinal Chemistry Letters, 14(13), 3545-3548. https://doi.org/10.1016/j.bmcl.2004.04.039