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Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation
Author(s) -
Park Yongho,
Koga Yumi,
Su Cindy,
Waterbury Amanda L.,
Johnny Christopher L.,
Liau Brian B.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201901386
Subject(s) - cycloheximide , protein biosynthesis , translation (biology) , elongation , polysome , protein synthesis inhibitor , chemistry , eukaryotic translation , ribosome , elongation factor , biochemistry , microbiology and biotechnology , biology , rna , messenger rna , materials science , ultimate tensile strength , metallurgy , gene
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. Described here is the total synthesis of CHX and analogues, and the establishment of 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.