A Versatile Synthetic Route to Cycloheximide and Analogues that Potently Inhibit Translation Elongation

Angewandte Chemie
Yongho ParkBrian Liau

Abstract

Cycloheximide (CHX) is an inhibitor of eukaryotic translation elongation that has played an essential role in the study of protein synthesis. Despite its ubiquity, few studies have been directed towards accessing synthetic CHX derivatives, even though such efforts may lead to protein synthesis inhibitors with improved or alternate properties. Here, we describe the total synthesis of CHX and analogues, and establish structure-activity relationships (SAR) responsible for translation inhibition. The SAR studies aided the design of more potent compounds, one of which irreversibly blocks ribosomal elongation, preserves polysome profiles, and may be a broadly useful tool for investigating protein synthesis.

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Citations

Dec 8, 2020·Biochemistry. Biokhimii︠a︡·S E DmitrievK A Lashkevich
Jun 9, 2021·Nature Communications·Chen ChenWei Min
May 19, 2021·European Journal of Pharmacology·Jianzhen LeiLan Luo
Oct 5, 2019·Journal of Natural Products·Di ZhangBin Wu

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