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ID: ALA4765410

Journal: Eur J Med Chem

Title: A cell-penetrant lactam-stapled peptide for targeting eIF4E protein-protein interactions.

Authors: Gallagher EE,Menon A,Chmiel AF,Deprey K,Kritzer JA,Garner AL

Abstract: Eukaryotic translation initiation factor 4E (eIF4E) has emerged as a promising cancer therapeutic target due to its role in the initiation of cap-dependent translation, a process that is accelerated during tumorigenesis. To regulate the initiation of cap-dependent translation, eIF4E participates in protein-protein interactions (PPI) with binding partners, 4E-BP1 and eIF4G, which act as an inhibitor and stimulator of translation, respectively. As both of these proteins interact with eIF4E by utilizing a short, α-helical stretch of amino acids, our laboratory has been working to develop helical mimetics of these proteins, in particular 4E-BP1, to inhibit eIF4E PPIs. Herein, we describe our continued efforts in this area and report the development and characterization of a cell-penetrant lactam stapled peptide for targeting cellular eIF4E.

CiteXplore: 32739551

DOI: 10.1016/j.ejmech.2020.112655