1407510-76-2Relevant academic research and scientific papers
ENTEROBACTIN CONJUGATES AND USES THEREOF
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Paragraph 0325; 0327, (2015/04/21)
The present invention provides novel enterobactin-cargo conjugates, such as compounds of Formula (I), and salts thereof, where X is the cargo and may be an antibiotic, a fluorophore, or biotin. The present invention also provides complexes, compositions, kits, and methods that involve the compounds of Formula (I) and are useful in delivering a cargo to a bacterium, treating a bacterial infection, cystic fibrosis, and/or inflammatory bowel disease in a subject, preventing a bacterial infection, cystic fibrosis, and/or inflammatory bowel disease in a subject, inhibiting the growth of or killing a bacterium, or determining the concentration of a bacterium in a biological sample. In certain embodiments, the bacterium is a Gram-negative bacterium.
Siderophore-mediated cargo delivery to the cytoplasm of escherichia coli and pseudomonas aeruginosa: Syntheses of monofunctionalized enterobactin scaffolds and evaluation of enterobactin-cargo conjugate uptake
Zheng, Tengfei,Bullock, Justin L.,Nolan, Elizabeth M.
, p. 18388 - 18400 (2013/01/15)
The design and syntheses of monofunctionalized enterobactin (Ent, l- and d-isomers) scaffolds where one catecholate moiety of enterobactin houses an alkene, aldehyde, or carboxylic acid at the C5 position are described. These molecules are key precursors to a family of 10 enterobactin-cargo conjugates presented in this work, which were designed to probe the extent to which the Gram-negative ferric enterobactin uptake and processing machinery recognizes, transports, and utilizes derivatized enterobactin scaffolds. A series of growth recovery assays employing enterobactin-deficient E. coli ATCC 33475 (ent-) revealed that six conjugates based on l-Ent having relatively small cargos promoted E. coli growth under iron-limiting conditions whereas negligible-to-no growth recovery was observed for four conjugates with relatively large cargos. No growth recovery was observed for the enterobactin receptor-deficient strain of E. coli H1187 (fepA-) or the enterobactin esterase-deficient derivative of E. coli K-12 JW0576 (fes-), or when the d-isomer of enterobactin was employed. These results demonstrate that the E. coli ferric enterobactin transport machinery identifies and delivers select cargo-modified scaffolds to the E. coli cytoplasm. Pseudomonas aeruginosa PAO1 K648 (pvd-, pch-) exhibited greater promiscuity than that of E. coli for the uptake and utilization of the enterobactin-cargo conjugates, and growth promotion was observed for eight conjugates under iron-limiting conditions. Enterobactin may be utilized for delivering molecular cargos via its transport machinery to the cytoplasm of E. coli and P. aeruginosa thereby providing a means to overcome the Gram-negative outer membrane permeability barrier.
