Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life.
Eur J Med Chem
; 152: 358-369, 2018 May 25.
Article
em En
| MEDLINE
| ID: mdl-29738954
ABSTRACT
Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61⯱â¯0.03 to 1.35⯱â¯0.21⯵M with the peptide γTatM4) and Gram-negative (MICs 0.71⯱â¯0.005 to 1.26⯱â¯0.02⯵M with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Peptidomiméticos
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Bactérias Gram-Negativas
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Bactérias Gram-Positivas
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article