A postdoctoral position in Organic and Medicinal Chemistry is open in the team "Metals and Microorganisms: Biology, Chemistry and Applications" (MMBCA).
Antibiotic resistance is a growing phenomenon and will constitute a major challenge in the coming decades. The development of new strategies to combat infections is therefore an urgent necessity, particularly against Gram-negative bacteria (GNB). The low permeability of the envelope of these bacteria constitutes the first line of defense against antibiotics. Nutrient assimilation systems constitute breaches in this rampart for those who know how to exploit them. The assimilation pathways of iron, a crucial element for bacterial proliferation, are particularly promising targets. The majority of bacteria thus excrete siderophores, iron(III) chelating metabolites, to chelate this metal in the extracellular environment. The ferric siderophore is then recognized and transported into the bacteria by a specific transmembrane mechanism involving several proteins. The conjugation of an antibiotic to a siderophore leads to the hijacking of these nutrient assimilation pathways to more effectively penetrate antibiotics into bacteria using the Trojan Horse strategy. As part of the RHEINGOLD project, we wish to vectorize antibacterial gold(I) complexes that have difficulty penetrating GNBs using siderophores. The recruited person will be responsible for preparing (synthesis and hemisynthesis), purifying and characterizing the siderophore vectors, under the direction of Dr. Gaëtan Mislin (HDR University of Strasbourg, DR CNRS). The gold(I) complexes will be prepared by our collaborator in Caen (LCMT, ENSICaen) and the conjugation between the two chemical entities will be the subject of close collaboration between the two teams. The siderophore-gold(I) conjugates will then be tested within the National Reference Center for Antibiotic Resistance (Besançon).
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