Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs.
Bioorg Med Chem
; 9(10): 2601-8, 2001 Oct.
Article
em En
| MEDLINE
| ID: mdl-11557348
ABSTRACT
The 16S bacterial ribosomal A-site decoding rRNA region is thought to be the pharmacological target for the aminoglycoside antibiotics. The clinical utility of aminoglycosides could possibly depend on the preferential binding of these drugs to the prokaryotic A-site versus the corresponding A-site from eukaryotes. However, quantitative aminoglycoside binding experiments reported here on prokaryotic and eukaryotic A-site RNA constructs show that there is little in the way of differential binding affinities of aminoglycosides for the two targets. The largest difference in affinity is 4-fold in the case of neomycin, with the prokaryotic A-site construct exhibiting the higher binding affinity. Mutational studies revealed that decoding region constructs retaining elements of non-Watson-Crick (WC) base pairing, specifically bound aminoglycosides with affinities in the muM range. These studies are consistent with the idea that aminoglycoside antibiotics can specifically bind to RNA molecules as long as the latter have non-A form structural elements allowing access of aminoglycosides to the narrow major groove.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Ribossômico
/
Canamicina
/
Aminoglicosídeos
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos