Combinatorial chemistry. Facing the challenge of chemical genomics
Ferenc Darvas, Gyorgy Dorman, Laszlo Urge, Istvan Szabo, Zsolt Ronai, and Maria Sasvari-Szekely
Pure Appl. Chem., Vol. 73, No. 9, pp. 1487-1498, 2001 Abstract
In the age of high-throughput screening and combinatorial chemistry, the focus of drug discovery is to replace the sequential approach with the most effective parallel approach. By the completion of the human gene-map, understanding and healing a disease require the integration of genomics, proteomics, and, very recently, metabolomics with early utilization of diverse small-molecule libraries to create a more powerful "total" drug discovery approach.
In this post-genomic era, there is an enhanced demand for information-enriched combinatorial libraries which are high-quality, chemically and physiologically stable, diverse, and supported by measured and predicted data. Furthermore, specific marker libraries could be used for early functional profiling of the genome, proteome, and metabolome. In this new operating model, called "combinatorial chemical genomics", an optimal combination of the marker and high-quality libraries provides a novel synergy for the drug discovery process at a very early stage. Full Text (PDF)
Solid phase synthesis of aryl-ether dendrimers
Andrea Basso, Brian Evans, Neil Peggb and Mark Bradley
Department of Chemistry, University of Southampton, Highfield, Southampton, UK SO 17 1BJ.
Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, UK SG1 2NY. Abstract
Solid phase chemistry can be used to prepare, in excellent yield and purity, a range of Frechet-type aryl-ether dendrimers, for use in either dendrimer conjugation studies, resin loading enhancement or the wedge based synthesis of larger dendrimers. Full Text (PDF)
Dynamic Combinatorial Chemistry
Ivan Hue and Regis Nguyen
Combinatorial Chemistry & High Throughput Screening, 2001, 109-130 Abstract
Dynamic combinatorial chemistry is based on the reversible combination of initial building blocks to form dynamic combinatorial libraries. It has recently emerged as an efficient strategy to detect and to evaluate affinity between the library products and a target molecule. In this review, examples from various fields of chemistry and biochemistry are presented and extensively discussed. The last section deals with the practical aspects for implementing this approach. Full Text (PDF)
Phenotypic Screening of Small Molecule Libraries by High Throughput Cell Imaging
J.C. Yarrow, Y. Feng, Z.E. Perlman, T. Kirchhausen and T.J. Mitchison
Combinatorial Chemistry & High Throughput Screening, 2003, 6, 79-99 Abstract
We have developed high throughput fluorescence cell imaging methods to screen chemical libraries for compounds with effects on diverse aspects of cell physiology. We describe screens for compounds that arrest cells in mitosis, that block cell migration, and that block the secretory pathway. Each of these screens yielded specific inhibitors for research use, and the mitosis screen identified Eg5 as a potential target protein for cancer chemotherapy. Cell imaging provides a large amount of information from primary screening data that can be used to distinguish compounds with different effects on cells, and together with automated analysis, to quantitate compound effects. Full Text (PDF)
Concepts of combinatorial chemistry and combinatorial technologies
Stanislav Miertus, Giorgio Fassina and P. F. Seneci
Chem. Listy 94, 1104 - 1110 (2000) Abstract
Combinatorial Chemistry and Combinatorial Technology (CC/CT) are a new interdisciplinary field joining computer-assisted combinatorial chemistry with automated parallel synthesis of chemical "libraries" followed by automated screening. Full Text (PDF)
