Issue 3, 2018

Exploring eukaryotic versus prokaryotic ribosomal RNA recognition with aminoglycoside derivatives

Abstract

New derivatives of aminoglycosides containing 6′-carboxylic acid or 6′-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure–activity relationships, along with the comparative molecular dynamics simulations within the eukaryotic rRNA decoding site, showed high sensitivity of 6′-position to substitution, indicating that the rational design of potent stop-codon read-through inducers requires consideration of not only the structure and energetics of the drug–RNA interaction but also the dynamics associated with that interaction.

Graphical abstract: Exploring eukaryotic versus prokaryotic ribosomal RNA recognition with aminoglycoside derivatives

Supplementary files

Article information

Article type
Research Article
Submitted
01 Jan 2018
Accepted
31 Jan 2018
First published
02 Feb 2018

Med. Chem. Commun., 2018,9, 503-508

Exploring eukaryotic versus prokaryotic ribosomal RNA recognition with aminoglycoside derivatives

N. M. Sabbavarapu, T. Pieńko, B. Zalman, J. Trylska and T. Baasov, Med. Chem. Commun., 2018, 9, 503 DOI: 10.1039/C8MD00001H

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