Structure-Activity Relationship Studies on the Inhibition of the Bacterial Translation of Novel Odilorhabdins Analogues
Bioorganic and Medicinal Chemistry
2020
Einārs Loža,
Matthieu Sarciaux,
Mārtiņš Ikaunieks,
Mārtiņš Katkevičs,
Tatjana Kukoša,
Nadezhda Trufilkina,
Viktorija Rjabova,
Kirill Shubin,
Lucile Pantel,
Marine Serri,
Douglas L. Huseby,
Sha Cao,
Kavita Yadav,
Karin Hjort,
Diarmaid Hughes,
Maxime Gualtieri,
Edgars Sūna,
Emilie Racine
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.
Keywords
Inhibition of bacterial translation, Novel amino acids, Novel antibiotic class, Odilorhabdins, SAR
DOI
10.1016/j.bmc.2020.115469
Hyperlink
https://www-sciencedirect-com.resursi.rtu.lv/science/article/pii/S0968089620302832?via%3Dihub
Loža, E., Sarciaux, M., Ikaunieks, M., Katkevičs, M., Kukoša, T., Trufilkina, N., Rjabova, V., Shubin, K., Pantel, L., Serri, M., Huseby, D., Cao, S., Yadav, K., Hjort, K., Hughes, D., Gualtieri, M., Sūna, E., Racine, E. Structure-Activity Relationship Studies on the Inhibition of the Bacterial Translation of Novel Odilorhabdins Analogues. Bioorganic and Medicinal Chemistry, 2020, Vol. 28, No. 11, Article number 115469. ISSN 0968-0896. e-ISSN 1464-3391. Available from: doi:10.1016/j.bmc.2020.115469
Publication language
English (en)