Combinatorial chemistry consists of an integrated series of new technologies for chemical design and production, much of which has been detailed elsewhere in this issue. Briefly, combinatorial chemistry involves the production of libraries of chemicals based on the controlled and sequential modification of generally immobilized or otherwise tagged chemical starting blocks. These original moieties are chosen, under optimal knowledge conditions, for their predicted or possible behavior in a functional drug, protein, polymer, or pesticide. Additional modifications or additions to the molecules at every stage produce geometric increases in the numbers of testable chemical candidates. Unlike traditional organic synthesis, it is the population phenomenon with all its attendant complexity that is the hallmark of combinatorial success.
Assays localize the optimal combinations produced, and purification and chemical analysis follow.
Many companies are pursuing the potential benefits of efficiently running the Red Queen's Race through the variable amalgam of directed drug design, combinatorial chemistry, and high-throughput screening. At each step of the way, knowledge of the biologies of the systems, the methods of automation, and the advanced technologies for computation and data mining are critical to handling such vast, complex arrays of information. Numerous start-up companies and corporate subsidiaries have decided to specialize in providing programs and services to fulfill these critical needs across a range of research venues. If you already know a great deal about these biological systems, then designing a combinatorial library is an easy task. In this case, the process can be narrowed down to modifications of specific chemical analogues that have the potential to interact with particular receptor sites.