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Updated: Sep 11, 2026

A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
Published on: January 17, 2014
Development of macrocyclic peptide inhibitors of Mycobacterium tuberculosis MurF via mRNA display with genetic
Patrick W Carlos1,2, Charlotte Franck1,2, Caitlin E Clarke-Shepperson1,2
1School of Chemistry, The University of Sydney Sydney NSW 2006 Australia richard.payne@sydney.edu.au.
Abstract:
The development of new antibacterials for Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains critical due to the continued global burden of disease and the emergence of multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. The MurF enzyme, which catalyses the ATP-dependent ligation of d-Ala-d-Ala to a UDP-MurNAc-tripeptide precursor in peptidoglycan biosynthesis, represents a promising therapeutic target. In this work, random non-standard peptide integrated discovery (RaPID) mRNA display with genetic reprogramming of a non-canonical uracil-derived amino acid was applied to Mtb MurF, leading to the identification of several high-affinity thioether-linked cyclic peptide ligands, several of which also inhibited the catalytic activity of the Mtb MurX enzyme.

