Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

de Lucio, H; Gamo, AM; Ruiz-Santaquiteria, M; de Castro, S; Sánchez-Murcia, PA; Toro, MA; Gutiérrez, KJ; Gago, F; Jiménez-Ruiz, A; Camarasa, MJ; Velázquez, S.
Improved proteolytic stability and potent activity against Leishmania infantum trypanothione reductase of α/β-peptide foldamers conjugated to cell-penetrating peptides.
Eur J Med Chem. 2017; 140(3):615-623 Doi: 10.1016/j.ejmech.2017.09.032
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Sánchez Murcia Pedro Alejandro
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: The objective of the current study was to enhance the proteolytic stability of peptide-based inhibitors that target critical protein-protein interactions at the dimerization interface of Leishmania infantum trypanothione reductase (Li-TryR) using a backbone modification strategy. To achieve this goal we carried out the synthesis, proteolytic stability studies and biological evaluation of a small library of α/β³-peptide foldamers of different length (from 9-mers to 13-mers) and different α→β substitution patterns related to prototype linear α-peptides. We show that several 13-residue α/β³-peptide foldamers retain inhibitory potency against the enzyme (in both activity and dimerization assays) while they are far less susceptible to proteolytic degradation than an analogous α-peptide. The strong dependence of the binding affinities for Li-TryR on the length of the α,β-peptides is supported by theoretical calculations on conformational ensembles of the resulting complexes. The conjugation of the most proteolytically stable α/β-peptide with oligoarginines results in a molecule with potent activity against L. infantum promastigotes and amastigotes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Amino Acid Sequence -; Animals -; Cell-Penetrating Peptides - administration & dosage; Cell-Penetrating Peptides - chemistry; Leishmania infantum - enzymology; NADH, NADPH Oxidoreductases - antagonists & inhibitors; Proteolysis -
Find related publications in this database (Keywords): alpha/beta-Peptides; Foldamers; Proteolysis; Protein-protein interactions; Trypanothione reductase; Leishmania infantum