A label for the bilirubin binding sites of human serum albumin was synthesized by reacting 2 mol of Woodward's reagent K (N-ethyl-5-phenylisoxazolium-3'-sulfonate) with 1 mol of bilirubin. This yielded a water-soluble derivative in which both carboxyl groups of bilirubin were converted to reactive enol esters. Covalent labeling was achieved by reacting the label with human serum albumin under n...

The nickel-containing enzyme urease is an essential colonization factor of the gastric pathogen Helicobacter pylori, as it allows the bacterium to survive the acidic conditions in the gastric mucosa. Although urease can represents up to 10% of the total protein content of H. pylori, expression of urease genes is thought to be constitutive. Here it is demonstrated that H. pylori regulates the ex...

The anticonvulsant lamotrigine is associated with idiosyncratic drug reactions, especially skin rashes. Most idiosyncratic reactions are believed to be caused by reactive metabolites. Previous studies have found evidence that an arene oxide is formed in rats; however, when we incubated radiolabeled lamotrigine with rat liver microsomes virtually no covalent binding was detected, and the expecte...

In the present work, the characterization of the biotransformation and bioactivation pathways of the cannabinoid receptor 1 antagonist rimonabant (Acomplia) is described. Rimonabant was approved in Europe in 2006 for the treatment of obesity but was withdrawn in 2008 because of a significant drug-related risk of serious psychiatric disorders. The aim of the present work is to characterize the b...

The controlled functionalization of single-walled carbon nanotubes (SWNTs) is a key to using them in high-end applications. We show that nanotube reactivity after covalent diazonium modification is governed by a chirality-specific surfactant binding affinity to SWNTs. Both metallic and semiconducting SWNTs tightly organized by a helical flavin mononucleotide (FMN) assembly exhibit two hundred t...

Cardiovascular implant mineralization involving bioprosthetic materials, such as glutaraldehyde cross linked porcine aortic valves or synthetic materials such as polyurethanes, is an important problem that frequently leads to clinical failure of bioprosthetic heart valves, and complicates long-term experimental artificial heart device implants. Novel, proprietary, calcification resistant polyet...

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are shown to be metabolized to covalent binding intermediates and various other metabolites by prostaglandin H synthase and horseradish peroxidase. BHA was extensively metabolized by horseradish peroxidase (80% conversion of parent BHA into metabolites) resulting in the formation of three dimeric products. O...

An in vitro screening model was developed to determine the reactivity of acyl glucuronide metabolites from carboxylic drugs. This assay is composed of two phases. The first is a phase of biosynthesis of acyl glucuronides by human liver microsomes (HLM). The second, during which acyl glucuronides are incubated with human serum albumin (HSA), consists of assessing the reactivity of acyl glucuroni...

Studies with two uropathogenic urease-producing Escherichia coli strains, 1021 and 1440, indicated that the urease genes of each are distinct. Recombinant plasmids encoding urease activity from E. coli 1021 and 1440 differed in their restriction endonuclease cleavage sites and showed minimal DNA hybridization under stringent conditions. The polypeptides encoded by the DNA fragments containing t...

Urease has been covalently immobilized on polypyrrole microspheres chemically linked to conducting polypyrrole-polyvinyl sulfonate (PPY-PVS) films. These films were electrochemically prepared during 5 7 min at a constant current of 2 mA using indium tin oxide (ITO) glass plates as the working electrode, and a standard calomel electrode as the reference electrode. Urease covalently linked to pol...