Jamal El Bakali, Michal Blaszczyk, Joanna C Evans, Jennifer A Boland, William J McCarthy, Imam Fathoni, Marcio V B Dias, Eachan O Johnson, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, Chris Abell, Christina Spry
The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by Mycobacterium tuberculosis ( Mtb ). Seeking to identify inhibitors of Mtb phosphopantetheine adenylyltransferase ( Mtb PPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the Mtb PPAT active site, presenting a unique opportunity for fragment linking...
April 17, 2023: Angewandte Chemie