Exploring eukaryotic versus prokaryotic ribosomal RNA recognition with aminoglycoside derivatives.
Medchemcomm
; 9(3): 503-508, 2018 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-30108940
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.
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MEDLINE
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En
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Medchemcomm
Ano de publicação:
2018
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Article