Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis, remains one of the leading causes of mortality across the world. There is an urgent requirement to build a robust arsenal of effective antimicrobials, targeting novel molecular mechanisms to overcome the challenges posed by the increase of antibiotic resistance in TB. Mycobacterium tuberculosis has a unique cell envelope structure and composition, containing a peptidoglycan layer that is essential for maintaining cellular integrity and for virulence. The enzymes involved in the biosynthesis, degradation, remodelling and recycling of peptidoglycan have resurfaced as attractive targets for anti-infective drug discovery. Here, we review the importance of peptidoglycan, including the structure, function and regulation of key enzymes involved in its metabolism. We also discuss known inhibitors of ATP-dependent Mur ligases, and discuss the potential for the development of pan-enzyme inhibitors targeting multiple Mur ligases.

Room temperature RAFT polymerisation for the design of multiblock acrylate/acrylamide copolymers.

A library of cationic polyacrylamide homopolymers was synthesized and their gene delivery, endosomal release, and interaction with endosome-specific lipids were investigated. The guanidinium-containing polymers were most efficient.

copolymers (MBCPs) are emerging class of materials that are becoming more accessible in recent years. However, to date there is still a lack of fundamental understanding of their physical properties. In particular, the glass transition temperature (Tg) which is known to be affected by the phase separation has not been well characterised experimentally. To this end, we report the first experimental study on the evolution of the Tgs and the corresponding phase separation of linear MBCPs with increasing number of blocks whilst keeping the overall degree of polymerisation (DP) constant (DP = 200). Ethylene glycol methyl ether acrylate (EGMEA) and tert-butyl acrylate (tBA) were chosen as monomers for reversible addition-fragmentation chain transfer polymerization to synthesise MBCPs. We found the Tgs (as measured by Differential Scanning Calorimetry) of EGMEA and tBA segments within the MCBPs to converge with increasing number of blocks and decreasing block length, correlating with the loss of the heterogeneity as observed from Small Angel X-ray Spectroscopy (SAXS) analysis. The Tgs of the multiblock copolymers were also compared to the Tgs of the polymer blends of the corresponding homopolymers, and we found that Tgs of the polymer blends were similar to those of the respective homopolymers, as expected. SAXS experiments further demonstrated microphase separation of multiblock copolymers. This work demonstrates the enormous potential of multiblock architectures to tune the physical properties of synthetic polymers, by changing their glass transition temperature and their morphologies obtained from microphase separation, with domain sizes reaching under 10 nm.