Péter Ábrányi-Balogh (Author), Aaron Keeley (Author), György G. Ferenczy (Author), László Petri (Author), Tímea Imre (Author), Katarina Grabrijan (Author), Martina Hrast (Author), Damijan Knez (Author), Janez Ilaš (Author), Stanislav Gobec (Author), György Keserü M. (Author)

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.

Keywords

kovalentni inhibitor;heterociklični elektrofili;označevanje cisteina;kvaternizacija;MurA;covalent inhibitor;heterocyclic electrophiles;cysteine labelling;quaternization;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 615.4:54:615.28
COBISS: 132462339 Link will open in a new window
ISSN: 1424-8247
Views: 8
Downloads: 0
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Other data

Secondary language: Slovenian
Secondary keywords: Farmacevtska kemija;Bakterijska rezistenca;
Type (COBISS): Article
Pages: 10 str.
Volume: ǂVol. ǂ15
Issue: ǂiss. ǂ12, art. 1484
Chronology: 2022
DOI: 10.3390/ph15121484
ID: 17332121