(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

doi:10.1016/j.bmcl.2004.04.039

(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 journal › Article

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 (K_i), 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 language	English
Pages (from-to)	3545-3548
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2004.04.039
State	Published - Jul 5 2004
Externally published	Yes

Keywords

Opioid peptide

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10.1016/j.bmcl.2004.04.039

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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

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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.",

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(4-Carboxamido)phenylalanine is a surrogate for tyrosine in opioid receptor peptide ligands. / Dolle, Roland E.; Machaut, Mathieu; Martinez-Teipel, Blanca; Belanger, Serge; Cassel, Joel A.; Stabley, Gabriel J.; Graczyk, Thomas M.; DeHaven, Robert N.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 13, 05.07.2004, p. 3545-3548.

Research output: Contribution to journal › Article

TY - JOUR

T1 - (4-Carboxamido)phenylalanine is a surrogate for tyrosine in opioid receptor peptide ligands

AU - Dolle, Roland E.

AU - Machaut, Mathieu

AU - Martinez-Teipel, Blanca

AU - Belanger, Serge

AU - Cassel, Joel A.

AU - Stabley, Gabriel J.

AU - Graczyk, Thomas M.

AU - DeHaven, Robert N.

PY - 2004/7/5

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AB - (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.

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