application): This proposal aims to establish the feasibility of exploiting metal-siderophore transport systems in Mycobacterium tuberculosis as a route for the development of a new class of antibiotics. Mycobactins, exochelins, and other siderophores function to sequester essential metals, particularly iron, within bacteria. Their bactericidal activity against mycobacteria when complexed with toxic metals will be evaluated in normal and iron-deficient media. Existing proprietary solid-phase methodology will be adapted for the production of combinatorial libraries based on the mycobactins and the exochelins. The affinity of compounds in these libraries for toxic metals will be determined by novel high-throughput screening methods, and metal-siderophore complexes found to be stable will be assayed against a variety of bacterial strains to determine their potency as antibacterial agents.
NOT AVAILABLE
| Poreddy, Amruta R; Schall, Otto F; Marshall, Garland R et al. (2003) Solid-phase synthesis of methyl carboxymycobactin T 7 and analogues as potential antimycobacterial agents. Bioorg Med Chem Lett 13:2553-6 |
