title: Novel small molecule inhibitors of MDR Mycobacterium tuberculosis by NMR fragment screening of antigen 85C.
abstract: Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in multiple-drug-resistant cases. By combining fragment-based drug discovery with early whole cell antibacterial screening, we discovered novel ligand-efficient inhibitors of multiple-drug resistant Mycobacterium tuberculosis (Mtb), which bind to the substrate site of the Mtb protein antigen 85C, hitherto unused in Mtb chemotherapy.
authors.affiliation: Combinature Biopharm AG, Robert-Roessle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheich
authors.forename: Vera
authors.initials: V
authors.lastname: Puetter
authors.forename: Markus
authors.initials: M
authors.lastname: Schade
mesh_terms: D000217:Acyltransferases / Q000737:chemistry*; D000942:Antigens, Bacterial / Q000737:chemistry*; D000995:Antitubercular Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D020134:Catalytic Domain; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D000217:Acyltransferases; C119774:antigen 85C, Mycobacterium tuberculosis