Recent Progress in Combinatorial Solid Phase Synthesis: Techniques, Characterization and its Application in Drug Development

Combinatorial chemistry has rapidly evolved from its interest in the generation of large number of compounds for the discovery of actives amongst them in random screening procedure to a powerful designed combinatorial technology for the creation and optimization of pharmaceutical lead compounds to produce drug candidates. The introduction of solid phase synthesis methods has rich impulse in this field, through automation and miniaturization. This review summarizes the present techniques of solid phase synthesis associated with combinatorial chemistry. The conventional methods for the synthesis of peptide libraries on solid support are split and mix synthesis, pre-mixed synthesis and parallel synthesis. In order to fulfil the increasing demand of synthetic peptides, several techniques have been developed, for example, pin synthesis, tea-bag synthesis, photolithography, SPOT synthesis, microchip synthesis, nanotechnology, lab-on-a-chip and bioinformatics and further their deconvolution to access the contribution of every peptide to the desired biological activity. This review also discusses about the combinatorial peptide library characterization and purity as well as their applications in drug development.