High-Throughput Screening for Inhibitors of Sialyl- and Fucosyltransferases

Authors

  • Cory D. Rillahan,

    1. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
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  • Dr. Steven J. Brown,

    1. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
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  • Amy C. Register,

    1. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
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  • Prof. Hugh Rosen,

    1. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
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  • Prof. James C. Paulson

    Corresponding author
    1. Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
    • Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA)
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  • We thank Prof. R. Brossmer for an initial sample of CMP-FITCNeuAc, Prof. L. Comstock for the FKP expression plasmid, Dr. C. Rademacher for bioinformatics and data analysis, and Dr. M. O’Reilly for assistance in our screening efforts. This work was supported by the NIH (T32 AI007606, R01AI050143, MH-084512).

Abstract

original image

Sweet screens: A high-throughput screening platform for identification of inhibitors of sialyl- and fucosyltransferases based on fluorescence polarization (FP) has been developed. An analogue of the natural donor substrate carrying a fluorescent label (green star) is transferred to a glycoprotein acceptor, which results in robust FP (see picture). The screening of 16 000 compounds against different glycosyltransferases has identified various interesting inhibitors.

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