title: Synthesis of ramariolide natural products and discovery of their targets in mycobacteria.
abstract: Ramariolides A-D are natural products with antibacterial activity. To exploit their cellular mechanism, we here devise the first total synthesis and prepare a photoprobe for target identification. Antibacterial testing against several pathogenic strains including Mycobacterium tuberculosis revealed the highest potency for ramariolide A. Chemical proteomics unraveled binding to essential proteins for amino acid anabolism.
authors.affiliation: Department of Chemistry, Center for Integrated Protein Science Munich (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany. stephan.sieber@tum.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Catalysis Research Center (CRC), Technische Universität München, Ernst-Otto-Fischer Straße 1, 85747 Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Richers
authors.affiliation: Catalysis Research Center (CRC), Technische Universität München, Ernst-Otto-Fischer Straße 1, 85747 Garching, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pöthig
authors.affiliation: Department of Chemistry, Center for Integrated Protein Science Munich (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany. stephan.sieber@tum.de.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Sieber
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D005227:Fatty Acids