Using Peptoid Libraries [Oligo N-Substituted Glycines] for Drug Discovery

This chapter explores the use of peptoid libraries ‘oligo n-substituted glycines’ for drug discovery. A series of compounds for solid-phase synthesis have been prepared with functional groups similar to or identical to the natural amino acids. In general, either reductive amination, route A, or alkylation, route B, provide the necessary monomers. They are then incorporated into a growing peptide/peptoid chain using the activating agents BOP or PyBroP under conditions similar to the Merrifield approach to peptide synthesis. Yields and characteristics of the products are analogous to those of peptides. Oligomeric N substituted glycines (NSG) peptoids and peptide/peptoid chimeras have been prepared with activity in several different bioassays. Synthesis can also be accomplished using a different scheme. The NSG oligomer can be thought of as an alternating copolymer of acetate/amine units rather than an oligomer of NSG units. The submonomers can be sequentially reacted to give a growing peptoid chain identical to that synthesized by traditional Merrifield methods.