Document Type
Article
Publication Date
1-22-2024
Publication Title
International Journal of Molecular Science
Volume
25
Issue
2
Pages
1-22
Publisher Name
MDPI
Abstract
Based on our previous success in using cyclobutanone derivatives as enzyme inhibitors, we have designed and prepared a 37-member library of α-aminocyclobutanone amides and sulfonamides, screened for inhibition of the bacterial enzyme diaminopimelate desuccinylase (DapE), which is a promising antibiotic target, and identified several inhibitors with micromolar inhibitory potency. Molecular docking suggests binding of the deprotonated hydrate of the strained cyclobutanone, and thermal shift analysis with the most potent inhibitor (3y, IC50 = 23.1 µM) enabled determination of a Ki value of 10.2 +/− 0.26 µM and observed two separate Tm values for H. influenzae DapE (HiDapE).
Recommended Citation
Habeeb Mohammad, Thahani Shifna; Kelley, Emma H.; Reidl, Cory T. Dr.; Konczak, Katherine; Beulke, Megan; Javier, Janielle; Olsen, Ken W.; and Becker, Daniel P. Ph.D.. Cyclobutanone Inhibitors of Diaminopimelate Desuccinylase (DapE) as Potential New Antibiotics. International Journal of Molecular Science, 25, 2: 1-22, 2024. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.3390/ijms25021339
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Statement
© The Authors, 2024.
Comments
Author Posting © The Authors, 2024. This is an open access article published by the International Journal of Molecular Science, Volume 25, Issue 2. https://doi.org/10.3390/ijms25021339