Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes.
Lanqing YingHongkun ZhuMarina Y FossoSylvie Garneau-TsodikovaKurt FredrickPublished in: Antibiotics (Basel, Switzerland) (2020)
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 C12 or C14 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.
Keyphrases
- pseudomonas aeruginosa
- induced apoptosis
- cell cycle arrest
- nucleic acid
- acinetobacter baumannii
- drug delivery
- copy number
- single molecule
- ionic liquid
- biofilm formation
- transcription factor
- gene expression
- drug resistant
- cystic fibrosis
- drug release
- multidrug resistant
- cancer therapy
- oxidative stress
- binding protein
- cell proliferation
- escherichia coli
- hyaluronic acid
- cell death
- pi k akt
- structure activity relationship