Combinatorial Chemistry & High Throughput Screening - Volume 7, Issue 2, 2004

The quantitative structure-activity relationship (QSAR) of a set of 29 agonists for tyramine (TA) receptor responsible for the inhibition of sex-pheromone production in Plodia interpunctella, was analyzed using comparative receptor surface analysis (CoRSA). Using the common steric and electrostatic features of the most active members of a series of compounds, CoRSA generated a virtual receptor model, represented as Read More

We have developed a method of spraying assay reagents onto a target gel in the Micro-Arrayed Compound Screening (μARCS) format. After application of target gels to compound sheets, subsequent reagents can be applied by spraying onto the target gel. The spraying method conserves on assay reagents by up to 10-fold, eliminates the need for casting additional agarose gels, and increases the throughput of a Read More

Enzymes can perform intricate regioselective and / or enantioselective chemical transformations and can accelerate reaction rates by enormous factors all under mild conditions. However, enzymes almost always present problems for use on an industrial scale. Evolutionary design approaches can be applied to the generation of stable enzymes with improved or novel catalytic activities. Directed evolution can be considered as t Read More

Motivation: Microarrays have allowed the expression level of thousands of genes or proteins to be measured simultaneously. Data sets generated by these arrays consist of a small number of observations (e.g., 20-100 samples) on a very large number of variables (e.g., 10,000 genes or proteins). The observations in these data sets often have other attributes associated with them such as a class label denoting the pathol Read More

To meet growing needs for high throughput gene expression profiling, we established a new automated high throughput TaqMan RT-PCR method for quantitative mRNA expression analysis. In this method, the AllegroTM (Zymark) system conducts all sample tracking and liquid handling steps, and ABI PRISM® 7900 HT (Applied Biosystems) is used to conduct real-time determination of the Ct value when amplification of PCR product Read More

Targeting of drugs and genes to specific cell types is an emerging paradigm in the treatment of many medical conditions. However, targeting structures such as peptides are susceptible to rapid inactivation in vivo. To address this problem, novel targeting molecules can now be rapidly synthesized using a combinatorial approach. Methods to screen the large libraries created in this process are often lacking or compatibl Read More

Capsazepine (CPZ, 1) is a well-known vanilloid receptor (VR1) antagonist that has been cited widely used inthe literature. However the current synthetic methods used for the total synthesis of CPZ are lengthy, involve multiple purification steps, and produce low yields. Here we describe a new and highly efficient synthesis of benzazepine 3, a synthetic precursor of CPZ, in only two steps and 59% overall yield from a comme Read More

The automated polymer-assisted solution phase (PASP) synthesis of a 72 member library of 2- alkylthio-benzimidazoles 16 and benzimidazolin-2-ones 17 using commercially available robotic workstations is described. By incorporating both automated aqueous work-ups, in-line scavenging and 'catch and release' protocols the desired compounds were obtained directly in good yields and excellent purities without the need for co Read More