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Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C(12) or C(14) linear alkyl substituents potently inhibit reverse t...

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Detalles Bibliográficos
Autores principales: Ying, Lanqing, Zhu, Hongkun, Fosso, Marina Y., Garneau-Tsodikova, Sylvie, Fredrick, Kurt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168264/
https://www.ncbi.nlm.nih.gov/pubmed/32098020
http://dx.doi.org/10.3390/antibiotics9020093
Descripción
Sumario:Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C(12) or C(14) linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles.