Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues.
Bioorg Med Chem
; 28(11): 115469, 2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32279921
ABSTRACT
A structure-activity relationship (SAR) study of NOSO-95179, a nonapeptide from the Odilorhabdin class of antibacterials, was performed by systematic variations of amino acids in positions 2 and 5 of the peptide. A series of non-proteinogenic amino acids was synthesized in high enantiomeric purity from Williams' chiral diphenyloxazinone by highly diastereoselective alkylation or by aldol-type reaction. NOSO-95179 analogues for SAR studies were prepared using solid-phase peptide synthesis. Inhibition of bacterial translation by each of the synthesized Odilorhabdin analogues was measured using an in vitro test. For the most efficient analogues, antibacterial efficacy was measured against two wild-type Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae) and against an efflux defective E. coli strain (ΔtolC) to evaluate the impact of efflux on the antibacterial activity.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Escherichia coli
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Klebsiella pneumoniae
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Antibacterianos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article