Combinatorial Chemistry & High Throughput Screening - Volume 6, Issue 1, 2003

Molecular modelling techniques have been used to screen zeolite catalysts for their suitability for organic synthesis. For example, we have used these techniques to study the alkylation of aromatic molecules which are important in the fine-chemical and drug industries. A survey of all such efforts is reviewed in this article. The application of molecular modelling techniques in a systematic manner is an efficient first step in th Read More

This review surveys the methods developed for the purification of intermediates and final compounds originating from parallel and combinatorial chemistry. Included will be reviews of polymerassisted purification, liquid-phase combinatorial chemistry, fluorous synthesis, liquid-liquid and solid-phase extraction, reverse-phase HPLC and supercritical fluid chromatography. A critique of each method is given, highlighting the metho Read More

Screening of phage display libraries allows rapid identification of peptides binding to a target. However, functional analysis of the phage sequences and their reproduction as soluble and stable peptides are often the most time-consuming part in the screening. We have used here intein-based peptide biosynthesis to produce a phage-display derived gelatinase inhibitory peptide CTTHWGFTLC and to identify the critical residues f Read More

A combinatorial library of 60 C- nucleoside analogs was synthesized by sequential coupling of building blocks followed by cyclative cleavage with DBU in an efficient manner. Only DMSO soluble compounds were tested for their modulatory effect against filarial γ-glutamyl cysteine synthetase (γ-GCase) and glutathione-S-transeferases (GSTs). Several compounds were found to be weak inhibitors of filarial γ-GCase, whereas, mo Read More

Improving on the poor success rates in the drug discovery industry requires that knowledge-based decisions are made to advance or stop a lead candidate as early as possible in the discovery process. Failure to make such timely decisions on the rigorous selection of lead candidates has costly time and resource implications in downstream drug development. To meet this challenge dedicated ‘hit to lead’ groups have recently be Read More

To validate potential application of phage display-antibody arrays for high-throughput screening on a novel proteomics biochip, we examined the epitopes versus the full protein of glucose-6-phosphatedehydrogenase (G6PD) from yeast. In a predictive approach, we used the Hopp-Woods method and compared the results with antibodies directed against the entire enzyme. In total, 16 peptides of a length of 11 amino acids Read More

Because of their biological activity, stability in vivo, the rigid spatial positioning of their substituents, and their synthetic challenges, heterocyclic aromates continue to be of interest to both academic and industrial medicinal chemists. Currently, many drug-like heterocyclic aromates are prepared via solidphase organic chemistry methods. This review examines the applicability of those methods towards combinatorial che Read More