Tagged versus untagged libraries: methods for the generation and screening of combinatorial chemical libraries

Over the past two decades the pharmaceutical industry has been driven by the biological sciences. The discovery and description of the biological mechanisms that underlie disease states accompanied by an unraveling of these mechanisms has provided drug, and more recently biotechnological, companies with a barrage of new therapeutic targets. Paradoxically, as a result of such biological and biochemical advances, new sources of drug leads are in short supply. Considerable efforts in trying to create potential drug candidates has led to the parturition of combinatorial chemical libraries. In this review I will examine some of the main technologies for generating and deducing active components from combinatorial libraries that have been segregated into two schools of thought: (i) the creation and decoding of combinatorial libraries by so-called tagged methodologies, and (ii) the production and deconvolution of chemical libraries by untagged protocols.