Next-generation heterocyclic electrophiles as small-molecule covalent MurA inhibitorsÁbrányi-Balogh, Péter (Avtor) Keeley, Aaron (Avtor) Ferenczy, György G. (Avtor) Petri, László (Avtor) Imre, Tímea (Avtor) Grabrijan, Katarina (Avtor) Hrast Rambaher, Martina (Avtor) Knez, Damijan (Avtor) Ilaš, Janez (Avtor) Gobec, Stanislav (Avtor) Keserü M., György (Avtor) covalent inhibitorheterocyclic electrophilescysteine labellingquaternizationMurAHeterocyclic 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.20222022-12-06 10:19:37Članek v reviji142958sl