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
Y1 - 2004/7/5
N2 - (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.
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.
KW - Opioid peptide
UR - http://www.scopus.com/inward/record.url?scp=2942615372&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2004.04.039
DO - 10.1016/j.bmcl.2004.04.039
M3 - Article
C2 - 15177470
AN - SCOPUS:2942615372
SN - 0960-894X
VL - 14
SP - 3545
EP - 3548
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 13
ER -