Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II.

Abstract

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.

• Authors: Jennifer M Chambers, Lisa M Lindqvist, Andrew Webb, David C S Huang, G Paul Savage, Mark A Rizzacasa
• Journal: Organic letters (Org Lett) Vol. 15 Issue 6 Pg. 1406-9 (Mar 15 2013) ISSN: 1523-7052 [Electronic] United States
• PMID: 23461621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Synthesis Inhibitors
• Triterpenes
• episilvestrol
• silvestrol
• Eukaryotic Initiation Factor-4A

Topics

• Animals
• Biotinylation
• Eukaryotic Initiation Factor-4A (antagonists & inhibitors)
• Humans
• Mice
• Protein Synthesis Inhibitors (chemistry, pharmacology)
• Triterpenes (chemical synthesis, chemistry, pharmacology)