Ammosamides A and B Target Myosin

Authors

  • Chambers C. Hughes Dr.,

    1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA), Fax: (+1) 858-534-1318
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  • John B. MacMillan Dr.,

    1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA), Fax: (+1) 858-534-1318
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  • Susana P. Gaudêncio Dr.,

    1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA), Fax: (+1) 858-534-1318
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  • William Fenical Prof. Dr.,

    1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA), Fax: (+1) 858-534-1318
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  • James J. La Clair Dr.

    1. Xenobe Research Institute, 3371 Adams Avenue, San Diego, CA 92116 (USA)
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  • This work was the result of financial support from the US National Cancer Institute (CA44848 to W.F.). S.P.G. is grateful to the Fundação para a Ciência e Tecnologia, Portugal, for a postdoc fellowship. The authors thank Sara Kelly (Scripps Institution of Oceanography) for cell culturing, Timothy Foley and Michael D. Burkart (University of California at San Diego) for assistance with the production of the XRI-TF35 mAb resin, and Qishan Lin (CFG at University of Albany) for protein ID analyses.

Abstract

original image

The protein target of the ammosamides, cytotoxic natural products from a marine-derived actinomycete, has been elucidated. An immunoaffinity fluorescent tag was used to construct a fluorescent molecular probe (see structure). First, uptake and localization of the probe in cells was visualized with fluorescence microscopy. The probe was then used to co-immunoprecipitate proteins that bound to the ammosamide core. Myosin was thus identified as a target.

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