The Development of a Beta-Sheet Mimic
Mentor 1
Trevor Hagemann
Start Date
14-6-2021 2:00 PM
Description
Gram negative bacteria have been found to be particularly resistant to antibiotic drugs due to an outer membrane that prevents the passage of typical antibacterial drugs into the cell. This outer membrane is composed in part of proteins that contain beta-barrels which are essential for cell viability. These are assembled by the beta-barrel assembly machine (BAM), which when inhibited will result in an unfolded BAM that will create an unregulated pore in the outer membrane allowing other antibiotic drugs to get into and kill the cell. A protein has been identified that inhibits the BAM complex, but proteins are not great as drugs because they are easily metabolized in the body. The goal of this project is to synthesize a compound that mimics a beta sheet in an analogous way as the protein. The target compound has been made through a low yielding and difficult sequence, so method development is still necessary. The goal of the work described here is to replicate this procedure on a model compound to determine the most ideal conditions for the sequence. After the synthesis is complete on the model, the sequence will be run on a precursor of the final product to hopefully produce the final product in high yield.
The Development of a Beta-Sheet Mimic
Gram negative bacteria have been found to be particularly resistant to antibiotic drugs due to an outer membrane that prevents the passage of typical antibacterial drugs into the cell. This outer membrane is composed in part of proteins that contain beta-barrels which are essential for cell viability. These are assembled by the beta-barrel assembly machine (BAM), which when inhibited will result in an unfolded BAM that will create an unregulated pore in the outer membrane allowing other antibiotic drugs to get into and kill the cell. A protein has been identified that inhibits the BAM complex, but proteins are not great as drugs because they are easily metabolized in the body. The goal of this project is to synthesize a compound that mimics a beta sheet in an analogous way as the protein. The target compound has been made through a low yielding and difficult sequence, so method development is still necessary. The goal of the work described here is to replicate this procedure on a model compound to determine the most ideal conditions for the sequence. After the synthesis is complete on the model, the sequence will be run on a precursor of the final product to hopefully produce the final product in high yield.
