ArticleNucleic acids research2020
Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Tied to Work: Topologically Knotted SPOUT Methyltransferases and UCH Deubiquitinases in Cellular Biochemistry.Journal of cellular biochemistry · 2026Review
- Nicotinamide-Based Covalent Inhibitors of tRNA (mACS medicinal chemistry letters · 2026Article
- Nanoscale Direct-to-Biology Optimization and Structural Insights into SelectiveJournal of medicinal chemistry · 2025Article
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery.Antibiotics (Basel, Switzerland) · 2023Review
- Implementation of a mycobacterial CRISPRi platform in Mycobacterium abscessus and demonstration of the essentiality of ftsZTuberculosis (Edinburgh, Scotland) · 2023Article
- tRNA methylation resolves codon usage bias at the limit of cell viability.Cell reports · 2022Article
- Fragment-Based Drug Discovery against Mycobacteria: The Success and Challenges.International journal of molecular sciences · 2022Review
- Chemical biology and medicinal chemistry of RNA methyltransferases.Nucleic acids research · 2022Article
- Potential therapeutic targets fromRSC medicinal chemistry · 2022Review
- Management ofEuropean respiratory review : an official journal of the European Respiratory Society · 2022Review
- Fragment-to-Lead Medicinal Chemistry Publications in 2020.Journal of medicinal chemistry · 2022Review
- Evolutionary repair reveals an unexpected role of the tRNA modification m1G37 in aminoacylation.Nucleic acids research · 2021Article
- Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.Medicinal research reviews · 2021Review
- A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway ofComputational and structural biotechnology journal · 2021Article
- Development of Inhibitors againstJournal of medicinal chemistry · 2019Article
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Authors and funding
17 authors.
Funding
Abstract
Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs.
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