MEPicides: α,β-unsaturated Fosmidomycin -Acyl Analogs as Efficient Inhibitors of 1-Deoxy-d-xylulose-5-phosphate reductoisomerase.

Malaria, a mosquito-borne disease caused by several parasites of the genus, remains a huge threat to global public health. There are an estimated 0.5 million malaria deaths each year, mostly among African children.

Spontaneous Selection of Drug Resistance in a Calf Model of Infection.

The intestinal protozoan is a leading cause of diarrheal disease and mortality in young children. There is currently no fully effective treatment for cryptosporidiosis, which has stimulated interest in anticryptosporidial development over the last ∼10 years, with numerous lead compounds identified, including several tRNA synthetase inhibitors. Here, we report the results of a dairy calf efficacy trial of the methionyl-tRNA ( MetRS [MetRS]) synthetase inhibitor 2093 and the spontaneous emergence of drug resistance.

Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.

With the rising prevalence of multidrug resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising potency but fail due to poor drug-like qualities (e.g.

Potent, specific MEPicides for treatment of zoonotic staphylococci.

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare.

MEPicides: α,β-Unsaturated Fosmidomycin Analogues as DXR Inhibitors against Malaria.

Severe malaria due to Plasmodium falciparum remains a significant global health threat. DXR, the second enzyme in the MEP pathway, plays an important role to synthesize building blocks for isoprenoids. This enzyme is a promising drug target for malaria due to its essentiality as well as its absence in humans.

Determination of single-cell oxygen consumption with impedance feedback for control of sample-probe separation.

The ability to measure chemical gradients surrounding single cells provides novel insights into several areas of cell dynamics--particularly metabolism. Detection of metabolic oxygen consumption can be achieved from a single mammalian cell using a modulated amperometric sensor in a self-referencing mode. To date, however, apart from visual cues, we do not have a reliable and cell-compatible method for determining and stabilizing the position of such probes.

Determination of 8-oxoguanine and 8-hydroxy-2'-deoxyguanosine in the rat cerebral cortex using microdialysis sampling and capillary electrophoresis with electrochemical detection.

A rapid and sensitive method to determine 8-oxoguanine (8oxoG) and 8-hydroxydeoxyguanosine (8OHdG), biomarkers for oxidative DNA damage, in cerebral cortex microdialysate samples using capillary electrophoresis (CE) with electrochemical detection (CEEC) was developed. Samples were concentrated on-column using pH-mediated stacking for anions. On-column anodic detection was performed with a carbon fiber working electrode and laser-etched decoupler.

On-column electrochemical detection for microchip capillary electrophoresis.

The development of a cellulose acetate decoupler for on-column electrochemical detection in microchip capillary electrophoresis is presented. The capillary based laser-etched decoupler is translated to the planar format to isolate the detector circuit from the separation circuit. The decoupler is constructed by aligning a series of 20 30-microm holes through the coverplate of the microchip with the separation channel and casting a thin film of cellulose acetate within the holes.