Presenter Information

Katherine TormaFollow

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

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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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.