Strategies for rapid deconvolution of combinational libraries: comparative evaluation using a model system

Journal of Medicinal Chemistry
D A KoningsS M Freier

Abstract

Synthesis and testing of complex mixtures maximize the number of compounds that can be prepared and tested in a combinatorial library. When mixtures of compounds are screened, however, the identity of the compound(s) selected may depend on the deconvolution procedure employed. Previously, we developed a model system for evaluation of deconvolution procedures and used it to compare pooling strategies for iterative and noniterative deconvolution [Freier et al. J. Med. Chem. 1995, 38, 344-352]. We have now extended the model studies to include simulations of procedures with overlapping subsets such as subtractive pooling [Carell et al. Angew, Chem., Int. Ed. Engl. 1994, 33, 2061-2064], bogus coin pooling [Blake and Litzi-Davis. Bioconjugate Chem. 1992, 3, 510-513], and orthogonal pooling [D'Prez et al. J. Am. Chem. Soc. 1995, 117, 5405-5406]. These strategies required synthesis and testing of fewer subsets than did the more traditional nonoverlapping iterative strategies. The compounds identified using simulations of these strategies, however, were not the most active compounds in the library and were substantially less active than those identified by simulations of more traditional strategies.

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Citations

Sep 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Rudresha KottaniAndrei G Kutateladze
Sep 10, 2014·Journal of Photochemistry and Photobiology. A, Chemistry·Roman N EzhovAndrei G Kutateladze
Dec 26, 2001·Journal of Mass Spectrometry : JMS·A TrioloC A Maggi
Jan 16, 2002·Journal of Receptor and Signal Transduction Research·P Seneci
Jul 13, 2004·Journal of Combinatorial Chemistry·Adi AkaviaRon Shamir
Dec 29, 2000·Journal of Combinatorial Chemistry·J TeixidoC M Tice
Nov 9, 2004·Journal of Combinatorial Chemistry·Ramakrishna Sasubilli, William G Gutheil

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