Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.

Protecting Group Control of Hydroxyketone-Hemiketal Tautomeric Equilibrium Enables the Stereoselective Synthesis of a 1-Azido -Nucleoside.

The synthesis of 1-azido -nucleosides is described to expand the set of azide-functionalized nucleosides for bioorthogonal applications and as potential antiviral drugs. Lewis acid-promoted azidation of a nucleoside hemiketal resulted in the formation of a tetrazole through a Schmidt reaction manifold. Conformational control to prevent ring-chain tautomerism enabled efficient 1-azidation with complete β-diastereoselectivity.

Thiol Stress Fuels Pyrazinamide Action Against .

Pyrazinamide (PZA) is a cornerstone of first-line antitubercular drug therapy and is unique in its ability to kill nongrowing populations of through disruption of coenzyme A synthesis. Unlike other drugs, PZA action is conditional and requires potentiation by host-relevant environmental stressors, such as low pH and nutrient limitation. Despite its pivotal role in tuberculosis therapy, the mechanistic basis for PZA potentiation remains unknown and the durability of this crucial drug is challenged by the emergent spread of drug resistance.

Evaluation of corn fermented protein on the fecal microbiome of cats.

Co-products from the ethanol industry, such as distillers dried grains with solubles (DDGS), can provide alternative protein sources for pet food. Corn fermented protein (CFP) is produced using postfermentation technology to split the protein and yeast from fiber prior to drying. This results in a higher protein ingredient compared to DDGS, increasing its appeal for pet food.

Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin.

Lipid biosynthesis in the pathogen Mycobacterium tuberculosis depends on biotin for posttranslational modification of key enzymes. However, the mycobacterial biotin synthetic pathway is not fully understood. Here, we show that rv1590, a gene of previously unknown function, is required by M.