Crystallographic screening for and hit expansion of P. aeruginosa FabF inhibitors – a possible starting point for novel antibiotics

A crystallographic fragment screen resulted in several FabF hits, binding to various pockets as well as the interface of the protein dimer. For two active site hits, a rudimentary hit expansion was carried out, exploring binding for the hits binding the malonyl sub-pocket. For the malonyl sub-pocket inhibitors, only weak affinity was observed, but the crystallographic data can conceivably guide future linking and merging strategies.