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A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

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Manresa Presas, Ma. Ángeles (María Ángeles)

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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.

# metadata.dc.rights[].value
cc-by-nc-nd (c) Rabanal Anglada, Francesc et al., 2015

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Articles publicats en revistes (Biologia, Sanitat i Medi Ambient)

# metadata.dc.title[].value
A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity