It is widely accepted that combinatorial chemistry was born in the early 1980s when Mario Geysen, then in Melbourne, Australia, invented the pin method in which simultaneous synthesis of diversified peptides gave rise to the first combinatorial libraries.
The use of combinatorial chemistry synthetic methods allow a very large number of molecules to be synthesised much more rapidly and at lower cost than traditional synthetic chemistry.
Combinatorial chemistry libraries are usually represented by one or more structures with a small number of R-group positions. For each R-group position there are lists of alternative groups.
Combinatorial library methods were first applied to peptides and oligonucleotides. Since then, the field has been expanded to include proteins, synthetic oligomers, small molecules, and oligosaccharides. The method of library preparation is dependent on the type of library desired. All combinatorial library methods involve three main steps: preparation of the library, screening of the library components, and determination of the chemical structures of active compounds.
The aim of chemical compound library design is to reduce the number of molecules, which need to be made without decreasing the
diversity of the library. This has the potential of finding leads more rapidly because a smaller number of
molecules are tested by avoiding molecules which are very similar.
