Combinatorial Chemistry & High Throughput Screening - Volume 10, Issue 4, 2007

Efficient compound selection remains a key challenge in drug discovery today. The goal is to identify developable drug candidates early in the screening process while simultaneously flagging compounds with off-target effects indicative of liabilities or alternate indications. This goal overlaps but is distinct from the goal of toxicogenomics which is focused primarily on identifying toxicity signatures of lead candidates in key tissu Read More

Based on the relative ratios of di- and tri-nucleotides in the DNA sequences, the profiles of 164 genome sequences from 152 representative microbial organisms were computed. By comparing the profiles of the genomes and their substrings with length 500 bps, the fluctuations of the relative abundances of di- and tri-nucleotides of these genomic sequences were analyzed. A new method to discriminate the origins of o Read More

The synthesis of 3-N-substituted-2-thioxoquinazoline-4-ones is described with a traceless linker strategy using poly(ethylene glycol) (PEG) as a soluble polymeric support. Staudinger-Aza-Wittig reaction of PEG-supported azide with Ph3P and CS2 gave the corresponding PEG-supported phenyl isothiocyanate. Treatment of the phenyl isothiocyanate with different primary amines led, via intramolecular cyclization and simultaneou Read More

Previously, we have reported the development and application of self-indicating resins (SIR), materials which can indicate presence or absence of amines in the reaction solution by the conspicuous color change of a phenolsulfophthalein type dye immobilized on resin beads [2a]. Although the functionality necessary for attaching the dye to the resins could be readily introduced by the Suzuki-Miyaura coupling during the synthes Read More

Recently, we established a robust method for the detection of hybridization events using a DNA microarray deposited on a nanoporous membrane. Here, in a follow-up study, we demonstrate the performance of this approach on a larger set of LNA-modified oligoprobes and genomic DNA sequences. Twenty-six different LNA-modified 7-mer oligoprobes were hybridized to a set of 66 randomly selected human genomic DNA Read More

In this paper, we (1) introduce a logical representation (LR) for DNA primary sequences; (2) show relations between LR and some other representations including the characteristic sequences of a DNA sequence, Randic's 2-D, 4-D representations, and Z-curve (a 3-D graphical representation); and (3) outline the constructions of the S/S matrix specific for a logical sequence and its 2*2 condensed matrix.

While significant investments are made across the industry and increasingly also in academia to enhance or build a compound file, the efficient sourcing of compounds from in-house medical chemistry is frequently seen as a challenge. This article introduces the Compound Hub strategy developed at the Novartis Compound Archive. Central Compound Hubs in Basel and Cambridge were combined with web-based orderin Read More

The second messenger cAMP has been implicated in numerous cellular processes such as glycogen metabolism, muscle contraction, learning and memory, and differentiation and development. Genetic evidence suggests that the enzyme that produces cAMP, adenylyl cyclase (AC), may be involved in pathogenesis in many of these cellular processes. In addition, these data suggest that membrane-bound ACs may be valuabl Read More