Targeting Aminoacyl tRNA Synthetases for Antimalarial Drug Development.
Annu Rev Microbiol
; 77: 111-129, 2023 09 15.
Article
en En
| MEDLINE
| ID: mdl-37018842
ABSTRACT
Infections caused by malaria parasites place an enormous burden on the world's poorest communities. Breakthrough drugs with novel mechanisms of action are urgently needed. As an organism that undergoes rapid growth and division, the malaria parasite Plasmodium falciparum is highly reliant on protein synthesis, which in turn requires aminoacyl-tRNA synthetases (aaRSs) to charge tRNAs with their corresponding amino acid. Protein translation is required at all stages of the parasite life cycle; thus, aaRS inhibitors have the potential for whole-of-life-cycle antimalarial activity. This review focuses on efforts to identify potent plasmodium-specific aaRS inhibitors using phenotypic screening, target validation, and structure-guided drug design. Recent work reveals that aaRSs are susceptible targets for a class of AMP-mimicking nucleoside sulfamates that target the enzymes via a novel reaction hijacking mechanism. This finding opens up the possibility of generating bespoke inhibitors of different aaRSs, providing new drug leads.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Aminoacil-ARNt Sintetasas
/
Malaria
/
Antimaláricos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Annu Rev Microbiol
Año:
2023
Tipo del documento:
Article