Combinatorial Chemistry & High Throughput Screening - Volume 9, Issue 1, 2006

With this issue Combinatorial Chemistry & High Throughput Screening begins its ninth year of publication. CCHTS continues to publish review articles and original research papers in all areas of combinatorial chemistry and high throughput screening. This issue, for example, contains both review articles (see the review by Hsieh, et al., of fast mass spectrometric assays that are being used to enhance the throughput of dru Read More

Historically, most bioanalytical methods for drug analysis in pharmaceutical industry were developed using HPLC coupled with UV or fluorescence detection. However, there is a trend toward interfacing separation technologies with more sensitive tandem mass spectrometry (MS/MS)-based systems. MS/MS detection offers complete resolution of the parent compounds from their first pass metabolites to avoid extra efforts fo Read More

The glycine transporter (GlyT-1b) is a Na+/Cl--dependent electrogenic transporter which mediates the rapid reuptake of glycine from the synaptic cleft. Based on its tissue distribution, GlyT-1 has been suggested to co-localise with the NMDA receptor where it may modulate the concentration of glycine at its co-agonist binding site. This data has led to GlyT-1 inhibitors being proposed as targets for disorders such as schizophrenia Read More

A simple and straightforward three-component methodology for the solution phase high-throughput synthesis of 2,5-disubstituted pyridazin-3(2H)-one libraries has been developed. The diversity at position 5 of the heterocycle is determined by the use of Suzuki, Sonogashira, Heck or Stille coupling.

Proteases play a key role in cell functions, and it is very important to monitor their activities for drug screening and diagnosis of diseases. In the present study, a new class of fluorescence probe, into which a fluorophore and a quencher have been introduced, was developed and applied to the on-chip detection of caspase-3 activity. This probe is non fluorescent in the absence of caspase-3. However, when it is treated with a Read More

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of the outer leaflet of the outermembrane of Gram-negative bacteria. Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient, worldwide. The sequestration of circulatory endotoxin may be a viable therapeutic strategy for the prophylaxis and treatment of Gram-n Read More

High Content Screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modelling systems. In this work, we compared a confocal and a non-confocal cellular HCS system, the IN Cell Analyzers1 3000™ and 1000™, respectively. As a cellular model system we used the Transfluor™ 2 technology i Read More

In this paper, a new protein coding gene-finding algorithm specific for the yeast genome at 96% accuracy is proposed. Five-fold cross-validation tests are performed to confirm the above accuracy. By the new algorithm, the number of protein coding genes in the yeast genome is re-estimated. The estimate is based on the assumption that the unknown genes have similar statistical properties to the known genes. It is Read More

Phage display is one of the best methods to identify drug targets, although technical problems including imprecision in quantifying phage and false-positive results are common. To address these difficulties, we propose two methods to more rapidly identify drug-binding phage particles. First, quantification of phage using SYBR Green Realtime PCR significantly improved accuracy and reproducibility. Second, affinity-column chr Read More

The oligosaccharide residue in glycoconjugates located in cell membranes is responsible for intercellular recognition and interaction: it acts as a receptor for proteins, hormones, and microorganisms and governs immune reactions. These significant activities have stimulated great interest in the field of oligosaccharides and glycoconjugates. Although many advances have been made in the synthesis of oligosaccharides, more Read More