Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues
| Autor: | Kirill Shubin, Douglas L. Huseby, Sha Cao, Martins Ikaunieks, Kavita Yadav, Emilie Racine, Martins Katkevics, Maxime Gualtieri, Diarmaid Hughes, Tatyana Kukosha, Matthieu Sarciaux, Karin Hjort, Marine Serri, Einars Loza, Nadezhda Trufilkina, Victoria Ryabova, Edgars Suna, Lucile Pantel |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Novel amino acids Clinical Biochemistry Pharmaceutical Science Peptide Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Biochemistry Inhibition of bacterial translation Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Prokaryotic translation Escherichia coli Peptide synthesis medicine Structure–activity relationship Novel antibiotic class Molecular Biology chemistry.chemical_classification Odilorhabdins Organisk kemi Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Anti-Bacterial Agents 0104 chemical sciences Amino acid Klebsiella pneumoniae 010404 medicinal & biomolecular chemistry chemistry Molecular Medicine Efflux Antibacterial activity Oligopeptides SAR |
| Popis: | 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 (Delta tolC) to evaluate the impact of efflux on the antibacterial activity. |
| Databáze: | OpenAIRE |
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