Chapter 208 - Mixture-Based Combinatorial Libraries

Abstract

This chapter focuses on the use of mixture-based combinatorial libraries. Mixture-based combinatorial libraries have many uses. They provide a fast inexpensive way to discover specific biologically active peptides. The two most widely used deconvolution strategies for mixture-based combinatorial libraries are iterative and positional scanning. The iterative deconvolution approach uses a step-by-step selection and enhancement process to identify individual compounds. The positional scanning deconvolution approach is a more rapid means to gather information about all possible variable positions in a soluble mixture library. A wide range of combinatorial libraries, from peptides to low-molecular-weight heterocyclic compounds, have been successfully screened in assays specific for the opioid receptors and have enabled the identification of new ligands for these receptors. New opioid peptides found from combinatorial libraries range in length from tetramers to decamers. Postsynthetic chemical modifications of resin-bound peptide libraries enables the generation of peptidomimetics and low-molecularweight heterocyclic combinatorial libraries.