[25] Synthesis of N-substituted glycine peptoid libraries

Oligomeric N-substituted glycines (NSG) or “peptoids” are a novel class of polymer that is ideally suited for the generation of diverse molecular libraries. The compounds are stable, easy to synthesize, and have potent biological activities. This chapter describes straightforward detailed protocols, for synthesizing diverse peptoid libraries, without any sophisticated equipment and with only a minimum of effort. In order for a class of molecules to be suitable for the generation of diverse libraries, ideally several criteria should be met. First, the compounds should be accessible, by solid-phase synthesis, to allow the resin-splitting methods of equimolar mixture synthesis to be used. Second, molecules with an oligomeric architecture allow a variety of chemical functionalities to be incorporated into a molecule, with a single linking chemistry. This greatly simplifies the synthesis of libraries, especially with respect to automation. The efforts here are focused on the synthesis of NSG peptoid oligomers, because they fit the criteria just listed. These oligomers are structurally similar to peptides, but have several major differences.