Inhibitors of the Herbicidal Target IspD: Halogen Bonding in an Allosteric Pocket
Due to the dramatic development of resistance against herbicides, there is an urgent need for new products with novel modes of action. The enzyme IspD from the MEP-pathway leading to isoprenoids has been identified as such a new herbicidal target. Leads based on HTS-screening campaigns were binding in a newly formed allosteric pocket. Fine tuning halogen bonding interactions, potent inhibitors could be developed and characterized with a series of crystal structures. The mechanism of inhibition could be further analyzed with mutations in the active site and a hypothesis for the function of this allosteric pocket could be developed.