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Elongation factors are a specialized group of proteins essential for the elongation phase of protein biosynthesis, facilitating the sequential addition of amino acids to a growing polypeptide chain. In prokaryotes, the primary factors include EF-Tu, which escorts aminoacyl-tRNA to the ribosome, and EF-G, which drives the translocation of the ribosome along the mRNA (UniProt, 2024). Eukaryotic cells utilize analogous factors such as eEF1A and eEF2, which are frequently overexpressed in various malignancies and serve as potential targets for anti-cancer therapies like plitidepsin (PubMed, 2021). These factors are also the primary targets for several potent antibiotics and toxins; for example, fusidic acid inhibits bacterial EF-G to treat Staphylococcal infections, while diphtheria toxin lethally inactivates eEF2 through ADP-ribosylation (NIH, 2023). Beyond their role in translation, elongation factors are increasingly recognized for non-canonical functions in cell signaling, apoptosis, and viral replication, making them versatile targets in infectious disease and oncology.
Drugs targeting elongation factors typically inhibit protein synthesis by either preventing the delivery of aminoacyl-tRNA to the ribosomal A-site (e.g., EF-Tu inhibitors), blocking the translocation of the mRNA-tRNA complex (e.g., EF-G or eEF2 inhibitors), or inducing the permanent inactivation of the factor through covalent modification such as ADP-ribosylation (StatPearls, 2023; UniProt, 2024).
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