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Analitical techniques in combinatorial chemistry - Swarth M.E.

Swarth M.E. Analitical techniques in combinatorial chemistry - Marcel Dekker, 2000. - 311 p.
ISBN 0-8247-1939-5
Download (direct link): analyticaltechniquesincombinatorialchemistry2000.pdf
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LC characterization of combinatorial libraries is a vital tool in drug discovery, and, in one format or another, will remain so for a long time. High throughput methods, open access environments, mass directed auto-purification, and total system integration have lead to increased utilization of LC in ways that a few short years ago were unimaginable. This trend can only continue, as researchers strive for higher throughput, and wider applicability in solving challenges in drug discovery.
The author would like to acknowledge the contributions of Chris Chumsae, Andrew Brailsford, Jeffrey Holyoke, and Beverly Kenney of Waters Corporation who collaborated in various ways in the data generated for use in this chapter.
Liquid Chromatography
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Capillary Electrophoresis in Combinatorial Library Analysis
Ira S. Krull
Northeastern University Boston, Massachusetts
Christina A. Gendreau
Waters Corporation Milford, Massachusetts
Hong Jian Dai
Shuster Laboratories Quincy, Massachusetts
Although capillary electrophoresis (CE),1 also known as high-performance CE or HPCE, has been known and described in the literature for almost two decades, its use for combinatorial mapping is much more recent (1-14). There does not appear to be a previous review, other than that in Analytical Chemistry (an American Chemical Society journal), that describes the general applicability and applications of CE for these purposes (15). There are relatively few actual publications in the refereed literature that have utilized various CE modes to perform analysis of combinatorial maps. At the same time, there are
1 All acronyms and abbreviations are defined in the glossary preceding the references.
Krull et al.
many more CE papers that have used affinity recognition to identify an active antigen or antibody or receptor molecule, but not as part of a larger library of similarly structured compounds. Most papers in the literature deal with the synthesis and characterization of libraries in terms of chemical structures, not biological activity (15-17). Because sections of this book are devoted to analytical approaches to screen compounds in combinatorial libraries for activity, it represents the first major effort to describe how analytical chemistry can be applied to identify individual, active members of a chemical library. In this chapter, the focus is on describing how CE approaches (methods, instrumentation, protocols, techniques) can be applied to a combinatorial library and isolate, as well as characterize, only those active (lead) compounds in a given library. This is quite different from characterizing all of the members of a given library in terms of their individual structures or saying that a given structure is present in a particular library.
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