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SHR Neuro Cancer Cardio Lipid Metab Microb

Ruiz-Santaquiteria, M; Sánchez-Murcia, PA; Toro, MA; de Lucio, H; Gutiérrez, KJ; de Castro, S; Carneiro, FAC; Gago, F; Jiménez-Ruiz, A; Camarasa, MJ; Velázquez, S.
First example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antileishmanial activity^{.

Eur J Med Chem. 2017; 135(19):49-59
Doi: 10.1016/j.ejmech.2017.04.020
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Co-authors Med Uni Graz: Sánchez Murcia Pedro Alejandro
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Abstract:: A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH₂ (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization. Cyclic analogues 3 and 4 were more resistant to proteases than was the linear prototype. Furthermore, the most potent TryR inhibitors in the linear and cyclic series displayed potent in vitro activity against Leishmania infantum upon conjugation with cationic cell-penetrating peptides. To date, these conjugated peptides can be considered the first example of TryR dimerization inhibitors that are active in cell culture. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Cell Proliferation - drug effects; Cells, Cultured -; Dimerization -; Dose-Response Relationship, Drug -; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Leishmania infantum - cytology; Leishmania infantum - drug effects; Leishmania infantum - metabolism; Molecular Dynamics Simulation -; Molecular Structure -; NADH, NADPH Oxidoreductases - antagonists & inhibitors; NADH, NADPH Oxidoreductases - metabolism; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; Structure-Activity Relationship -
Find related publications in this database (Keywords): Peptides; Helix stabilization; Protein-protein interactions; Trypanothione reductase; Leishmania infantum; Cell-penetrating peptides