Creation of a Tailored Aldolase for the Parallel Synthesis of Sialic Acid Mimetics

Authors

  • Thomas Woodhall,

    1. School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK, Fax: (+44) 113-233-6565
    2. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
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  • Gavin Williams Dr.,

    1. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
    2. School of Biochemistry and Microbiology, University of Leeds, Leeds, LS2 9JT, UK
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  • Alan Berry Dr.,

    1. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
    2. School of Biochemistry and Microbiology, University of Leeds, Leeds, LS2 9JT, UK
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  • Adam Nelson Dr.

    1. School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK, Fax: (+44) 113-233-6565
    2. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
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Abstract

original image

Broadening substrate specificity: A modified form of sialic acid aldolase (E192N) exhibits a 640-fold switch in substrate specificity relative to the wild-type enzyme. Ozonolysis of the unsaturated amides 1, followed by an E192N-mediated step, was exploited in the parallel synthesis of 14 different sialic acid mimetics of general structure 2.

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