2021
DOI: 10.1128/aac.00300-21
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RNase P Inhibitors Identified as Aggregators

Abstract: RNase P is an essential enzyme responsible for tRNA 5'-end maturation. In most bacteria, the enzyme is a ribonucleoprotein consisting of a catalytic RNA subunit and a small protein cofactor termed RnpA. Several studies reported small molecule inhibitors directed against bacterial RNase P that were identified by high-throughput screenings. Using the bacterial RNase P enzymes from Thermotoga maritima, Bacillus subtilis and Staphylococcus aureus as model systems, we found that such compounds, including RNPA2000 a… Show more

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Cited by 4 publications
(2 citation statements)
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“…Synthetic substrates derived from minihelices or bipartite pre-tRNAs severed at the anticodon loop have also been employed with end-attached fluorophore/quencher pairs. However, promising RNase P targeting drugs were recently identified as protein aggregators that do not inhibit RNase P with specificity, which calls into question their mode of action in vivo ( 109 ).…”
Section: Emerging Areas For Explorationmentioning
confidence: 99%
“…Synthetic substrates derived from minihelices or bipartite pre-tRNAs severed at the anticodon loop have also been employed with end-attached fluorophore/quencher pairs. However, promising RNase P targeting drugs were recently identified as protein aggregators that do not inhibit RNase P with specificity, which calls into question their mode of action in vivo ( 109 ).…”
Section: Emerging Areas For Explorationmentioning
confidence: 99%
“…Additionally, RNPA2000 was reported to show weak RNase P inhibitory activity (IC 50 : 125 μM, Figure ). A concern for the identified RNase P inhibitors, including RNPA2000, iriginol hexaacetate, and purpurin, was that they acted as aggregators and are likely unspecific RNase P inhibitors. , In addition to small molecules, a FRET assay was employed to evaluate rationally designed and modified oligonucleotides as inhibitors of RNase P. Antisense oligonucleotides targeting the RNA component of RNase P were coupled to cell-penetrating peptides to yield conjugates that inhibited bacterial growth. The best-performed conjugates showed IC 50 values of ∼100 nM, being the most potent RNase P inhibitors reported to date …”
Section: Small-molecule Inhibitors Of Bacterial Rnasesmentioning
confidence: 99%