Combinatorial chemistry chemical diversity

Davies K. Using pharmacophore diversity to select molecules to test from commercial catalogues. In Chaiken IM and Janda KD, editors. Molecular diversity and combinatorial chemistry. Libraries and drug discovery. Washington DC American Chemical Society, 1996 309-16. 

While this may in fact be the case for natural product mixtures, it is rarely the case when dealing with synthesized mixtures. Despite our attempts to create real molecular diversity in the test tube, our efforts have not even begun to anticipate the true diversity of atomic connectivity within "drug space" (estimated to be of the order of 1063 unique compounds, theory, famously in this case, greatly outpacing the amount of matter in the universe). Thus, combinatorial chemistry was never practically able to produce true chemical diversity and compounds produced in such library format ended up looking very much like one another, with the attendant similarities in biological activity profiles. 

Pirrung, M.C., Chau, J.H.-L., and Chen, J., Indexed combinatorial libraries nonoligomeric chemical diversity for the discovery of novel enzyme inhibitors, in Combinatorial Chemistry, Wilson, S.R. and Czarnik, A.W., Eds., Wiley, New York, 1997, pp. 191-206. 

Advances in chemical synthesis have enabled considerable sophistication in the construction of diverse compound libraries to probe protein function [61, 62). However, few general techniques exist that can directly assess binding mechanisms and evaluate ligand afEnities in a multiplexed format. To realize the full potential of combinatorial chemistry in the drug discovery process, generic and efficient tools must be applied that combine mixture-based techniques to characterize protein-ligand interactions with the strengths of diversity-oriented chemical synthesis. 

Combinatorial chemistry is both the philosophical and the practical method with which to create structurally diverse compound libraries. Combinatorial chemistry is defined as that branch of synthetic organic chemistry that enables the concomitant synthesis of large numbers of chemical variants in such a manner as to permit their evaluation, isolation, and identification. Combinatorial chemistry affords techniques for the systematic creation of large but structurally diverse libraries. From a technical perspective, there are several avenues of approach to library creation ... 

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