Perez Fernandez, Déborah
Leong, Ng C.
Dubbaka, Srinivas R.
Böttger, Erik C.
- Journal Article
Rights / licenseCreative Commons Attribution 3.0 Unported
Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4′,6′-O-acetal and 4′-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4′-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets. Show more
Journal / seriesNature Communications
Pages / Article No.
PublisherNature Publishing Group
Organisational unit03425 - Chen, Peter / Chen, Peter
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