Presenter Information

Megan BeulkeFollow

Major

Chemistry

Anticipated Graduation Year

Spring 2022

Access Type

Open Access

Abstract

In our medicinal organic chemistry research lab, I am performing a ninhydrin-based enzyme inhibition assay, previously developed in our lab, to discover novel antibiotics to combat antibiotic resistance that poses an imminent public health crisis. These drugs target the bacterial enzyme N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE), a crucial enzyme to bacterial survival due to its involvement in the biosynthetic pathway of lysine, an amino acid essential to protein synthesis and mDAP, which is essential for bacterial cell wall construction. This pathway is exclusive to bacteria and is not found in mammalian cells, thus inhibition of this enzyme should be selectively toxic to bacteria. The assay enables testing of potential new inhibitors of DapE, done by spectrophotometric analysis of the products of the in vitro enzyme assay, quantitatively analyzing the amount of enzyme substrate converted to product. The goal is to evaluate several newly discovered inhibitor series involving indoline sulfonamides, tetrazoles, and N-aryl sulfonamides. Studying analogs of these compounds will greatly aid our understanding of the enzyme dynamics involved in the inhibition process. This information will broaden our understanding of the enzyme’s catalytic machinery to significantly aid in our future endeavors of drug synthesis and drug discovery for the optimization of new inhibitors.

Faculty Mentors & Instructors

Dr. Daniel P. Becker, Department of Chemistry and Biochemistry, Loyola University Chicago; Thahani S. Habeeb Mohammad, Chemistry Graduate Student LUC; Emma Kelley, Chemistry Graduate Student LUC

Supported By

Members of the Becker Research Lab

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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Evaluation of Various Analogs of High-Throughput Screening Target Molecules as DapE Inhibitors Using the DapE Ninhydrin Assay for Novel Antibiotic Discovery

In our medicinal organic chemistry research lab, I am performing a ninhydrin-based enzyme inhibition assay, previously developed in our lab, to discover novel antibiotics to combat antibiotic resistance that poses an imminent public health crisis. These drugs target the bacterial enzyme N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE), a crucial enzyme to bacterial survival due to its involvement in the biosynthetic pathway of lysine, an amino acid essential to protein synthesis and mDAP, which is essential for bacterial cell wall construction. This pathway is exclusive to bacteria and is not found in mammalian cells, thus inhibition of this enzyme should be selectively toxic to bacteria. The assay enables testing of potential new inhibitors of DapE, done by spectrophotometric analysis of the products of the in vitro enzyme assay, quantitatively analyzing the amount of enzyme substrate converted to product. The goal is to evaluate several newly discovered inhibitor series involving indoline sulfonamides, tetrazoles, and N-aryl sulfonamides. Studying analogs of these compounds will greatly aid our understanding of the enzyme dynamics involved in the inhibition process. This information will broaden our understanding of the enzyme’s catalytic machinery to significantly aid in our future endeavors of drug synthesis and drug discovery for the optimization of new inhibitors.