Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase

David A. Robinson, Paul G. Wyatt (Lead / Corresponding author)

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    1 Citation (Scopus)

    Abstract

    Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor of TbNMT, has been identified in previous studies; however, poor central nervous system exposure restricts its use to the haemolymphatic form (stage 1) of the disease. In order to identify new chemical matter, a fragment screen was carried out by ligand-observed NMR spectroscopy, identifying hits that occupy the DDD85646 binding site. Crystal structures of hits from this assay have been obtained in complex with the closely related NMT from Leishmania major, providing a structural starting point for the evolution of novel chemical matter.

    Original languageEnglish
    Pages (from-to)586-593
    Number of pages8
    JournalActa Crystallographica Section F: Structural Biology Communications
    Volume71
    Issue number5
    DOIs
    Publication statusPublished - May 2015

    Keywords

    • African trypanosomiasis
    • Molecular parasitology - advances in biology and supporting drug discovery
    • N-myristoyltransferase
    • Trypanosoma brucei

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