Targeting Rpf-interacting protein A (RipA) from M. tuberculosis using a fragment-based drug design approach

Despite being one of the oldest and further studied diseases of mankind, tuberculosis remains as the top cause of mortality among bacterial infections worldwide. Therefore, the search for new strategies to combat the pathogen in both active and dormant stages is needed. The endopeptidase Rpf-interacting protein A (RipA) is a secreted protein responsible for hydrolysing peptideoglican cross-links in Mycobacterium tuberculosis. Because RipA may participate on mycobacteria reactivation and it is essential for normal cell division, this enzyme has becoming an attractive target in the scope of drug discovery against tuberculosis. In the present study, we set out to identify the first leading compounds targeting RipA by applying the Fragment-Based Drug Discovery technique. The protein was screened against a fragment library by thermal-shift assay. A total of fifty-four fragments were identified as possible ligands, which are being tested for interaction validation.
This research is being supported by FAPESP grant 2016/18721-4.