A target engagement assay to assess uptake, potency and retention of antibiotics in living bacteria

A major challenge in antibiotics drug discovery is to turn potent biochemical inhibitors of essential bacterial components into effective antimicrobials. This difficulty is underpinned by a lack of methods to investigate the physicochemical properties needed for candidate antibiotics to permeate the bacterial cell envelope and avoid clearance by the action of bacterial efflux pumps. To address these issues, here we used a target engagement assay to measure the equilibrium and kinetics binding parameters of antibiotics to their molecular targets in live bacteria. We validated this approach for a known antibiotic target, dihydrofolate reductase, using the Gram-negative bacteria Escherichia coli and the emerging human pathogen Mycobacterium abscessus. We expect the use of similar target engagement assays to expedite the discovery and progression of novel, cell-permeable antibiotics with on-target activity.

Improved tight-binding parameters of III-V semiconductor alloys and their application to type-II superlattices

A simple tight-binding method for ternary semiconductor alloys is generalized to calculate the properties of the semiconductor alloys accurately. Specifically independently adjustable parameters, which represent compositional disorder, are incorporated in all the ternary tight-binding parameters. Energy levels and effective masses agree well with the reference values only by the proposed method. We have applied the method to calculate the band gaps and a spectrum of the absorption coefficient of (InAs)/(GaInSb) type-II superlattices. The calculated band-gaps agree well with the experimental ones and we could well reproduce the shape of the absorption coefficient spectrum calculated by an empirical pseudopotential scheme.

How Does Glycation Affect Binding Parameters of the Albumin-Gliclazide System in the Presence of Drugs Commonly Used in Diabetes? In Vitro Spectroscopic Study

In this research, the selected drugs commonly used in diabetes and its comorbidities (gliclazide, cilazapril, atorvastatin, and acetylsalicylic acid) were studied for their interactions with bovine serum albumin—native and glycated. Two different spectroscopic methods, fluorescence quenching and circular dichroism, were utilized to elucidate the binding interactions of the investigational drugs. The glycation process was induced in BSA by glucose and was confirmed by the presence of advanced glycosylation end products (AGEs). The interaction between albumin and gliclazide, with the presence of another drug, was confirmed by calculation of association constants (0.11–1.07 × 104 M−1). The nature of changes in the secondary structure of a protein depends on the drug used and the degree of glycation. Therefore, these interactions may have an influence on pharmacokinetic parameters.

Edge-state influence on high-order harmonic generation in topological nanoribbons

The high-order harmonic generation in finite topological nanoribbons is investigated using a tight-binding approximation. The narrow, two-dimensional ribbons consist of hexagonal structures. A topological phase transition is defined by a sudden change of the topological invariant. In the bulk, this kind of phase transition might occur if an existing band gap closes and reopens again. Through the bulk-boundary correspondence, this is related to the emergence of topologically protected edge states in the respective finite systems. For the finite ribbons studied in this work, the variation of the tight-binding parameters leads to the emergence of two edge states after the closing of the band gap. The energies of those edge states as functions of the tight-binding parameters display crossings and avoided crossings, which influence the high-harmonic spectra. Graphic Abstract