The development of low molecular weight anionophores is an emerging topic in chemistry, as the need for these compounds increases with the continuous discovery of pathologies involving anomalies in anion transport processes. Development of new concepts to initiate anion imbalance in living cells while fighting multidrug-resistant bacteria is a paramount topic. In this study, three series of compounds including N,N'-diphenylethynylbenzyl benzimidazolium salts (1 and 2), 1,1'-(pyridine-2,6-diyl)bis(3-(4-(phenylethynyl)benzyl)-1H-benzo[d]imidazol-3-ium) salts (3-5), and 1,1'-(pyridine-2,6-diylbis(methylene))bis(3-(4-(phenyl ethynyl)benzyl)-1H-benzo[d]imidazol-3-ium) salts (6-8) displaying high antimicrobial activity and low toxicity against human cells were designed, synthesized, and studied. The most potent compound displayed micromolar minimal inhibitory concentrations in different Gram-negative and Gram-positive bacteria, while its hemolytic activity remained around 10% or less, even after a prolonged period of exposure. The mechanism of action of these benzimidazolium salts on bacterial membrane was assessed by bioanalytical techniques including assays in model membrane liposomes, membrane depolarization studies, and scanning electron microscopy (SEM) in living bacteria.
Viral membrane proteins are prime targets in combatting infection. Still, the determination of their structure remains a challenge, both with respect to sample preparation and the need for structural methods allowing for analysis in a native-like lipid environment. Cell-free protein synthesis and solid-state NMR spectroscopy are promising approaches in this context, the former with respect to its great potential in the native expression of complex proteins, and the latter for the analysis of membrane proteins in lipids. Herein, we show that milligram amounts of the small envelope protein of the duck hepatitis B virus (DHBV) can be produced by cell-free expression, and that the protein self-assembles into subviral particles. Proton-detected 2D NMR spectra recorded at a magic-angle-spinning frequency of 110 kHz on <500 μg protein show a number of isolated peaks with line widths comparable to those of model membrane proteins, paving the way for structural studies of this protein that is homologous to a potential drug target in HBV infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.