Use of a fluorescence assay to determine relative affinities of semisynthetic aminoglycosides to small RNAs representing bacterial and mitochondrial A sites
The off-target binding of aminoglycosides (AGs) to the A site of human mitochondrial
ribosomes in addition to bacterial ribosomes causes ototoxicity and limits their potential as
antibiotics. A fluorescence assay was employed to determine relative binding affinities of
classical and improved AG compounds to synthetic RNA constructs representing the
bacterial and mitochondrial A sites. Results compared well with previously reported in vitro
translation assays with engineered ribosomes. Therefore, the minimal RNA motifs and …
ribosomes in addition to bacterial ribosomes causes ototoxicity and limits their potential as
antibiotics. A fluorescence assay was employed to determine relative binding affinities of
classical and improved AG compounds to synthetic RNA constructs representing the
bacterial and mitochondrial A sites. Results compared well with previously reported in vitro
translation assays with engineered ribosomes. Therefore, the minimal RNA motifs and …
Abstract
The off-target binding of aminoglycosides (AGs) to the A site of human mitochondrial ribosomes in addition to bacterial ribosomes causes ototoxicity and limits their potential as antibiotics. A fluorescence assay was employed to determine relative binding affinities of classical and improved AG compounds to synthetic RNA constructs representing the bacterial and mitochondrial A sites. Results compared well with previously reported in vitro translation assays with engineered ribosomes. Therefore, the minimal RNA motifs and fluorescence assay are shown here to be useful for assessing the selectivity of new compounds.
Elsevier
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