Identification and Characterization of New Inhibitors of Fungal Homoserine Kinase

Authors

  • Dr. Gianfranco De Pascale,

    1. M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Emma J. Griffiths,

    1. M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    2. Michael Smith Laboratories, University of British Columbia, 301–2185 East Mall, Vancouver, BC, V6T 1Z4 (Canada)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Tushar Shakya,

    1. M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    Search for more papers by this author
  • Dr. Ishac Nazi,

    1. M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    Search for more papers by this author
  • Prof. Gerard D. Wright

    Corresponding author
    1. M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    • M. G. DeGroote Institute for Infectious Disease Research and Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5 (Canada), Fax: (+1) 905-528-5330
    Search for more papers by this author

Abstract

original image

The aspartate pathway in fungi is a well-validated antimicrobial target. Deletion of homoserine kinase (THR1) has been proven to lead to a chemical-synthetic lethal phenotype in the presence of several bioactive molecules. We have identified and characterized several Thr1 inhibitors that can be used in combination therapy against fungal infections.

Ancillary