Influence of 4'-O-Glycoside Constitution and Configuration on Ribosomal Selectivity of Paromomycin

Matsushita, Takahiko; Chen, Weiwei; Juskeviciene, Reda; Teo, Youjin; Shcherbakov, Dimitri; Vasella, Andrea; Böttger, Erik C; Crich, David

doi:10.1021/jacs.5b02248

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Matsushita, T., Chen, W., Juskeviciene, R., Teo, Y., Shcherbakov, D., Vasella, A., Böttger, E. C., & Crich, D. (2015). Influence of 4’-O-Glycoside Constitution and Configuration on Ribosomal Selectivity of Paromomycin. Journal of the American Chemical Society, 137, 7706–7717. https://doi.org/10.1021/jacs.5b02248

Abstract

A series of 20 4′-O-glycosides of the aminoglycoside antibiotic paromomycin were synthesized and evaluated for their ability to inhibit protein synthesis by bacterial, mitochondrial and cytosolic ribosomes. Target selectivity, i.e., inhibition of the bacterial ribosome over eukaryotic mitochondrial and cytosolic ribosomes, which is predictive of antibacterial activity with reduced ototoxicity and systemic toxicity, was greater for the equatorial than for the axial pyranosides, and greater for the d-pentopyranosides than for the l-pent