Journal article
Synthesis of biotinylated episilvestrol: Highly selective targeting of the translation factors eIF4AI/II
JM Chambers, LM Lindqvist, A Webb, DCS Huang, GP Savage, MA Rizzacasa
Organic Letters | AMER CHEMICAL SOC | Published : 2013
DOI: 10.1021/ol400401d
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. © 2013 American Chemical Society.
Grants
Awarded by NHMRC
Funding Acknowledgements
Financial support for this work was provided by a University of Melbourne Research Support Scheme Grant and NHMRC Program Grants (461221 and 1016701). L.M.L. is supported by an NHMRC Early Career Fellowship and a CIHR Postdoctoral Fellowship. J.M.C. thanks CRC for financial support. We are grateful to Prof. D. Vaux (WEHI) for helpful discussions and reagents. J.M.C. and L.M.L. contributed equally to this work.