70 KB332 KB59 KB199820252011Blanot, DidierGobec, StanislavTurk, SamoŽivec, Matejštevilka:1letnik:58str. 95-109ISSN:1318-0207COBISSID:2983025URN:URN:NBN:SI:doc-PKQ5B1DCenSlovenian Chemical SocietySlovensko kemijsko društvoActa chimica slovenicabakterijski peptidoglikanbiosintezainhibitorji MurEprotimikrobne učinkovineDesign and synthesis of new peptidomimetics as potential inhibitors of MurE|With the continuing emergence and spread of multidrug-resistant bacteria, there is an urgent need for the development of new antimicrobial agents. One possible source of new antibacterial targets is the biosynthesis of the bacterial cellwall peptidoglycan. The assembly of the peptide stem is carried out by four essential enzymes, known as the Mur ligases (MurC, D, E and F). We have designed and synthesised a focused library of compounds as potential inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE) from Staphylococcus aureus. This was achieved using two approaches: (i) synthesis of transition-state analogues based on the methyleneamino core; and (ii) synthesis of MurE reaction product analogues. Two methyleneamino-based compounds are identified as initial hits for inhibitors of MurEZaradi pojavljanja in širjenja bakterijskih sevov, ki so hkrati odporni na več vrst protimikrobnih učinkovin, obstaja velika potreba po razvoju novih zdravilnih učinkovin. Eden izmed pomembnih virov novih tarč za razvoj protimikrobnih učinkovin je biosinteza bakterijskega peptidoglikana. Biosintezo peptidne verige v peptidoglikanu katalizirajo encimi ligaze Mur (C,D, E in F), ki so nujni za bakterijsko preživetje. Načrtovali in sintetizirali smo serijo spojin kot potencialnih inhibitorjev UDP-N-acetilmuramoil-L-alanil-D-glutamat:L-lizin ligaze (MurE) iz Staphylococcus aureus. Pri tem smo uporabili dva pristopa: (i) sintezo metilenaminskih derivatov kot mimetikov prehodnega stanja in (ii) sintezo produktnih ananlogov reakcije MurE. Dve spojini z metilenaminskim ogrodjem sta primerni za nadaljni razvoj inhibitorjev MurETEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaSlovensko kemijsko društvo