(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 journalArticlepeer-review

26 Scopus citations


(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
Issue number13
StatePublished - Jul 5 2004


  • Opioid peptide


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