Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides |
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| Authors: | Stephen P. Muench Jozef Stec Ying Zhou Gustavo A. Afanador Martin J. McPhillie Mark R. Hickman Patty J. Lee Susan E. Leed Jennifer M. Auschwitz Sean T. Prigge David W. Rice Rima McLeod |
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| Affiliation: | 1. School of Biomedical Sciences, University of Leeds, Leeds, UK;2. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, United States;3. Department of Ophthalmology and Visual Sciences, Pediatrics (Infectious Diseases), Committees on Genetics, Immunology and Molecular Medicine, Institute of Genomics and Systems Biology and The College, The University of Chicago, Chicago, IL 60637, United States;4. Johns Hopkins School of Public Health, Rm. E5132, 615 N. Wolfe St., Baltimore, MD 21205, United States;5. Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, UK;6. Department of Discovery, Division of Experimental Therapeutics Walter Reed Army Institute of Research, Rm 2N61, 503 Robert Grant Avenue, Silver Spring, MD 20910, United states |
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| Abstract: | The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery. |
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| Keywords: | Enoyl reductase Triclosan Toxoplasma Plasmodium |
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