Antimicrobial resistance (AMR) is a serious problem for the public health threat of broad concern to countries and all sectors. [1] Bacteria cell wall biosynthesis is one of the most important targets for the antibacterial treatments. [2] Recent studies have shown that Mur ligases are essentials enzymes for growing cell walls. [3] Part of this biological process, MurC-F ligase catalyzes non-ribosomal bond formation for the addition of peptide moiety on peptidoglycan chain building block. They are essential for the bacteria survival and specific to prokaryotic cells. Mur ligase enzymes share similar amino acid regions, structural regions and their mechanisms are fully elucidated. [4] These similarities can be used to design new antibacterial agents targeting several enzymes at the same time. In this context, we aim to develop a small library of uridine diphosphate N-acetyl muramic acid (UDP MurNAc) analogues (Fig. 1.). Virtual screening has been made with crystallographic data of MurD ligase to obtain potential inhibitors. [5] Thanks to this model, various modifications have been investigated at different position of UDP-MurNAC analogues. Thus, herein, we will present the synthesis of those latter compounds which can obtain by CuAAc reaction and Pd(0) chemistry as key steps. Finally, all obtained derivatives were evaluated in vitro by one-pot Mur ligases assays. Data will be presented.

Conception of mur ligase analogues for antibacterial activity

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.