Combinatorial Chemistry & High Throughput Screening - Volume 12, Issue 3, 2009

The phenolic compounds produced by in vitro shoots of Brassica oleracea L. var. costata DC were screened by HPLC-DAD-MS/MS. Thirty seven compounds were characterized, which included chlorogenic acids, flavonoids (the majority of them were hydroxycinnamic acid esters of kaempferol and quercetin glycosides) and hydroxycinnamic acyl glycosides (with predominance of synapoyl gentiobiosides). The antioxi Read More

The neurotransmission mediated by γ-aminobutyric acid (GABA) in the mammalian brain is terminated by a family of four GABA transporters (GATs). Inhibition of GATs is currently used in the treatment of epilepsy and these proteins are generally considered as important drug targets. In this study, we perform the first elaborate pharmacological characterization of all four human GAT subtypes. We conduct the experiment Read More

For years, the physicochemical properties of drug candidates have been used to predict their in vivo pharmacokinetic behaviors. Several theories and empirical correlations have been established by various researchers with the overall goal of expediting the drug candidate selection process, with greater confidence and faster turnaround. This study describes a 96-well reverse phase HPLC method, simultaneously determining Read More

RNA triphosphatases are attractive and mostly unexplored therapeutic targets for the development of broad spectrum antiprotozoal, antiviral and antifungal agents. The use of malachite green as a readout for phosphatases is well characterized and widely employed. However, the reaction depends on high quantities of inorganic phosphate to be generated, which makes this assay not easily amenable to screening in 1536-w Read More

The laccase CotA from Bacillus subtilis was converted from a generalist, an enzyme with broad specificity, to a specialist, an enzyme with narrowed specificity. Laccases are members of the multicopper oxidase family and have many applications in biotechnology. To date, it has not been demonstrated that substrate specificity can be tapered for a laccase. Wild-type CotA oxidizes ABTS (ABTS = diammonium 2,2'-azino-bis( Read More

An effective parallel solid phase route to methylenesulfonamides and amides bearing a wide variety of substituents is described. The three key reaction steps were reductive amination of a haloheteroaromatic aldehyde onto a benzhydrylamine type polystyrene resin, sulfonamide or amide formation and palladium catalysed transformation of the remaining heteroaromatic halogen. A process of virtual library design and filte Read More

A multi-step NMR based screening assay is described for identifying and evaluating chemical leads for their ability to bind a target protein. The multi-step NMR assay provides structure-related information while being an integral part of a structure based drug discovery and design program. The fundamental principle of the multi-step NMR assay is to combine distinct 1D and 2D NMR techniques, in such a manner, that the inh Read More

Whole-cell patch-clamp-based electrophysiological techniques are powerful tools for examining the biophysical and pharmacological properties of ion channels. However, the recent validation of ion channels as novel drug targets necessitates the development of a faster screening method for ion channels. Therefore, we have developed a rapid, reliable, and sensitive cell-based high throughput screening (HTS) assay for T-type Read More

Virtual (database) screening (VS) of molecules promises to accelerate the discovery of new drugs and reduce costs by identifying molecules with high probabilities of binding to a target receptor. The large amount of available protein X-ray crystal structures, together with the development of more effective homology modelling techniques, has led recently to a steep increase in docking-based VS studies. This approach needs c Read More

Current advances of new technologies with robotic automated assays combined with highly selective and sensitive LC-MS enable high-speed screening of lead series libraries in many in vitro assays. In this review, we summarize state of the art high throughput assays for screening of key physicochemical properties such as solubility, lipophilicity, pKa, drug-plasma protein binding and brain tissue binding as well as in vitro A Read More