CHAPTER 4: Peptide Library Technologies: Mixture-Based Library Generation and Screening

Mixture-based combinatorial libraries were first described in the early 1990s and have since been used in a wide array of assay formats in many laboratories. These libraries allow thousands of compounds to be prepared and screened at a fraction of the time and cost required for individual compound arrays. Mixture-based libraries are synthesized on solid phase, but screened in solution. Peptides were the natural choice for the first combinatorial chemists, as they provided a sufficient variety of side chains to create a large diversity (20 l-amino acids), solid phase synthesis is performed in a linear fashion, and chemical reactions had already been pre-optimized. Additionally, short peptides with biological activity were available to demonstrate the power of the emerging libraries in screening assays. The introduction of mathematical theory and computational analyses combined with a program for dissemination of the libraries will influence of mixtures-based drug peptide discovery in the coming years.