Opening the amino acid toolbox for peptide-based NTS2-selective ligands as promising lead compounds for pain management.

Autor: Previti S; Research Group of Organic Chemistry, Vrije Universiteit Brussel, Brussels, Belgium.; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy., Desgagné M; Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Tourwé D; Research Group of Organic Chemistry, Vrije Universiteit Brussel, Brussels, Belgium., Cavelier F; Institut des Biomolécules Max Mousseron, IBMM, UMR 5247, CNRS, Université de Montpellier, ENSCM, Montpellier, France., Sarret P; Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Ballet S; Research Group of Organic Chemistry, Vrije Universiteit Brussel, Brussels, Belgium.
Jazyk: angličtina
Zdroj: Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2023 Jun; Vol. 29 (6), pp. e3471. Date of Electronic Publication: 2023 Jan 11.
DOI: 10.1002/psc.3471
Abstrakt: Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ-opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid-independent analgesic effects through the binding of two G protein-coupled receptors (GPCRs), NTS1 and NTS2. In the last decades, modified NT analogues have been proven to provide potent analgesia in vivo. However, selective NTS1 and nonselective NTS1/NTS2 ligands cause antinociception associated with hypothermia and hypotension, whereas selective NTS2 ligands induce analgesia without altering the body temperature and blood pressure. In light of this, various structure-activity relationship (SAR) studies provided findings addressing the binding affinity of ligands towards NTS2. Herein, we comprehensively review peptide-based NTS2-selective ligands as a robust alternative for future pain management. Particular emphasis is placed on SAR studies governing the desired selectivity and associated in vivo results.
(© 2022 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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