A Chemical Proteomic Strategy Reveals Inhibitors of Lipoate Salvage in Bacteria and Parasites

The development of safe anti-infectives requires strategies focusing on pathways solely present in pathogens. Following this principle, we here developed inhibitors of lipoic acid (LA) salvage which is crucial for the survival of LA auxotroph bacteria and parasites but non-essential in human cells. An LA based probe was effectively transferred on substrate proteins via lipoate protein ligase (LPL) and hence, their binding sites determined by mass-spectrometry.