Ábrányi-Balogh, Péter and Keeley, Aaron and Keserű, György Miklós (2022) Next-Generation Heterocyclic Electrophiles as Small-Molecule Covalent MurA Inhibitors. PHARMACEUTICALS, 15 (12). No.-1484. ISSN 1424-8247
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Abstract
Heterocyclic electrophiles as small covalent fragments showed promising inhibitory activity on the antibacterial target MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase, EC:2.5.1.7). Here, we report the second generation of heterocyclic electrophiles: the quaternized analogue of the heterocyclic covalent fragment library with improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH (L-glutathione) reactivity assay, and thrombin counter screen were also used to demonstrate and explain the improved reactivity and selectivity of the N-methylated heterocycles and to compare the two generations of heterocyclic electrophiles.
| Item Type: | Article |
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| Uncontrolled Keywords: | covalent inhibitor; heterocyclic electrophiles; cysteine labelling; quaternization; MurA |
| Subjects: | Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia |
| Depositing User: | Dr. Péter Ábrányi-Balogh |
| Date Deposited: | 30 Sep 2024 08:07 |
| Last Modified: | 30 Sep 2024 08:07 |
| URI: | https://real.mtak.hu/id/eprint/206503 |
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