ArticleNucleic acids research2008
Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- NewRSC medicinal chemistry · 2025Article
- Combination of compound screening with an animal model identifies pentamidine to prevent Chlamydia trachomatis infection.Cell reports. Medicine · 2024Article
- Tetracyclines activate mitoribosome quality control and reduce ER stress to promote cell survival.EMBO reports · 2023Article
- In Silico Exploration of the Trypanothione Reductase (TryR) ofInternational journal of molecular sciences · 2023Article
- Nanotechnological approaches for pentamidine delivery.Drug delivery and translational research · 2022Review
- Activation of the Mitochondrial Unfolded Protein Response: A New Therapeutic Target?Biomedicines · 2022Review
- Repurposing non-antifungal drugs auranofin and pentamidine in combination as fungistatic antifungal agents againstFrontiers in cellular and infection microbiology · 2022Article
- Structure-Activity Studies with Bis-Amidines That Potentiate Gram-Positive Specific Antibiotics against Gram-Negative Pathogens.ACS infectious diseases · 2021Article
- Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem-loop RNAs and their implications for functional cellular assays.RNA (New York, N.Y.) · 2021Article
- Tetracyclines promote survival and fitness in mitochondrial disease models.Nature metabolism · 2021Article
- Regulation of MALAT1 triple helix stability and in vitro degradation by diphenylfurans.Nucleic acids research · 2020Article
- Aminoacyl-tRNA synthetases.RNA (New York, N.Y.) · 2020Review
- Drug repurposing for antimicrobial discovery.Nature microbiology · 2019Review
- Fluorescent peptide displacement as a general assay for screening small molecule libraries against RNA.Organic & biomolecular chemistry · 2019Article
- Insights into antitrypanosomal drug mode-of-action from cytology-based profiling.PLoS neglected tropical diseases · 2018Article
- Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.Biochemistry · 2018Article
- Small Molecules Which Improve Pathogenesis of Myotonic Dystrophy Type 1.Frontiers in neurology · 2018Review
- Drugging tRNA aminoacylation.RNA biology · 2018Review
- Development of highly active anti-MedChemComm · 2017Article
- Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance.Nature microbiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selective and potent inhibition of mitochondrial translation in Saccharomyces cerevisiae by pentamidine suggests a novel antimicrobial action for this drug. Electrophoresis mobility shift assay, T1 ribonuclease footprinting, hydroxyl radical footprinting and isothermal titration calorimetry collectively demonstrated that pentamidine non-specifically binds to two distinct classes of sites on tRNA. The binding was driven by favorable entropy changes indicative of a large hydrophobic interaction, suggesting that the aromatic rings of pentamidine are inserted into the stacked base pairs of tRNA helices. Pentamidine binding disrupts the tRNA secondary structure and masks the anticodon loop in the tertiary structure. Consistently, we showed that pentamidine specifically inhibits tRNA aminoacylation but not the cognate amino acid adenylation. Pentamidine inhibited protein translation in vitro with an EC(50) equivalent to that binds to tRNA and inhibits tRNA aminoacylation in vitro, but drastically higher than that inhibits translation in vivo, supporting the established notion that the antimicrobial activity of pentamidine is largely due to its selective accumulation by the pathogen rather than by the host cell. Therefore, interrupting tRNA aminoacylation by the entropy-driven non-specific binding is an important mechanism of pentamidine in inhibiting protein translation, providing new insights into the development of antimicrobial drugs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.