Major
Chemistry
Anticipated Graduation Year
2021
Access Type
Open Access
Abstract
Due to the increase in antibacterial resistance, there is an urgent need for novel antibacterial drugs. The target enzyme for this project is the dapE-encoded bacterial enzyme N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE). The lysine pathway that the DapE enzyme is a part of is absent in mammals, thus DapE inhibitors should selectively target bacteria and will be lethal to bacteria with no mechanism-based toxicity in humans. DapE is a key enzyme in the lysine biosynthetic pathway and products of which are precursors in bacterial cell wall synthesis. Thus, DapE enzyme is an ideal novel antibiotic target. The lead molecules identified by the Becker lab via a High-Throughput screen include a tetrazole-based hit, (2-[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]-N-(1,3-thiazol-2-yl)propanamide). Synthesis of isosteric analogs of this lead molecule will be described.
Faculty Mentors & Instructors
Dr. Daniel Becker, Thahani S. Habeeb Mohammad
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Synthesis of Tetrazole-based DapE Inhibitors as Potential Antibiotics
Due to the increase in antibacterial resistance, there is an urgent need for novel antibacterial drugs. The target enzyme for this project is the dapE-encoded bacterial enzyme N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE). The lysine pathway that the DapE enzyme is a part of is absent in mammals, thus DapE inhibitors should selectively target bacteria and will be lethal to bacteria with no mechanism-based toxicity in humans. DapE is a key enzyme in the lysine biosynthetic pathway and products of which are precursors in bacterial cell wall synthesis. Thus, DapE enzyme is an ideal novel antibiotic target. The lead molecules identified by the Becker lab via a High-Throughput screen include a tetrazole-based hit, (2-[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]-N-(1,3-thiazol-2-yl)propanamide). Synthesis of isosteric analogs of this lead molecule will be described.