Synthesis of Biotinylated Episilvestrol: Highly Selective Targeting of the Translation Factors eIF4AI/II

Silvestrol (1) and episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer; however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstrated that eukaryotic initiation factors eIF4A...

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Bibliographic Details
Published in:Organic letters 2013-03, Vol.15 (6), p.1406-1409
Main Authors: Chambers, Jennifer M, Lindqvist, Lisa M, Webb, Andrew, Huang, David C. S, Savage, G. Paul, Rizzacasa, Mark A
Format: Article
Language:English
Subjects:
Animals
Biotinylation
Eukaryotic Initiation Factor-4A - antagonists & inhibitors
Humans
Mice
Protein Synthesis Inhibitors - chemistry
Protein Synthesis Inhibitors - pharmacology
Triterpenes - chemical synthesis
Triterpenes - chemistry
Triterpenes - pharmacology
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Summary:Silvestrol (1) and episilvestrol (2) are protein synthesis inhibitors, and the former has shown efficacy in multiple mouse models of cancer; however, the selectivity of these potent cytotoxic natural products has not been described. Herein, it is demonstrated that eukaryotic initiation factors eIF4AI/II were the only proteins detected to bind silvestrol (1) and biotinylated episilvestrol (9) by affinity purification. Our study demonstrates the remarkable selectivity of these promising chemotherapeutics.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol400401d