Title:
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A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity
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Author:
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Rabanal Anglada, Francesc; Grau Campistany, Ariadna; Vila Farrés, Xavier; González-Linares, J. (Javier); Borràs Suárez, Miquel; Vila Estapé, Jordi; Manresa Presas, Ma. Ángeles (María Ángeles); Cajal Visa, Yolanda
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Other authors:
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Universitat de Barcelona |
Abstract:
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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain. |
Subject(s):
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-Desenvolupament de medicaments -Membranes (Biologia) -Pèptids -Toxicitat dels medicaments -Antibiòtics -Bacteris patògens -Drug development -Membranes (Biology) -Peptides -Drug toxicity -Antibiotics -Pathogenic bacteria |
Rights:
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cc-by-nc-nd (c) Rabanal Anglada, Francesc et al., 2015
http://creativecommons.org/licenses/by-nc-nd/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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Nature Publishing Group
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