The study reports on a series of novel cyclopeptides based on the structure Tyr-[D-Lys-Phe-Phe-Asp]NH2, a mixed mu and kappa opioid receptor agonist with low nanomolar affinity, in which Phe4 residue was substituted by cyclic amino acids, such as Pro or its six-membered surrogates, piperidine-2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). All derivatives exhibited high mu- and moderate delta-opioid receptor affinity, and almost no binding to the kappa-opioid receptor. Conformational analysis suggested that the cis conformation of the peptide bond Phe3-Xaa4 influences receptor selectivity through the control of the position of Phe3 side chain. The results substantiate the use of the cycle-macrocyle scaffolds for fine-tuning receptor selectivity.

Adamska-Bartłomiejczyk, A., De Marco, R., Gentilucci, L., Kluczyk, A., Janecka, A. (2017). Design and characterization of opioid ligands based on cycle-in-macrocycle scaffold. BIOORGANIC & MEDICINAL CHEMISTRY, 25(8), 2399-2405 [10.1016/j.bmc.2017.02.057].

Design and characterization of opioid ligands based on cycle-in-macrocycle scaffold

DE MARCO, ROSSELLA;GENTILUCCI, LUCA;
2017

Abstract

The study reports on a series of novel cyclopeptides based on the structure Tyr-[D-Lys-Phe-Phe-Asp]NH2, a mixed mu and kappa opioid receptor agonist with low nanomolar affinity, in which Phe4 residue was substituted by cyclic amino acids, such as Pro or its six-membered surrogates, piperidine-2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). All derivatives exhibited high mu- and moderate delta-opioid receptor affinity, and almost no binding to the kappa-opioid receptor. Conformational analysis suggested that the cis conformation of the peptide bond Phe3-Xaa4 influences receptor selectivity through the control of the position of Phe3 side chain. The results substantiate the use of the cycle-macrocyle scaffolds for fine-tuning receptor selectivity.
2017
Adamska-Bartłomiejczyk, A., De Marco, R., Gentilucci, L., Kluczyk, A., Janecka, A. (2017). Design and characterization of opioid ligands based on cycle-in-macrocycle scaffold. BIOORGANIC & MEDICINAL CHEMISTRY, 25(8), 2399-2405 [10.1016/j.bmc.2017.02.057].
Adamska-Bartłomiejczyk, Anna; De Marco, Rossella; Gentilucci, Luca; Kluczyk, Alicja; Janecka, Anna
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/596593
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