Peptoids with substituents on the backbone carbons as conformationally constrained synthetic oligoamides

Abstract

Oligo(N-substituted glycine) (oligo-NSG), also known as peptoid, is a synthetic oligomer with high proteolytic stability and membrane permeability due to the N-substituted structures. These beneficial pharmacokinetic properties make the oligomer attractive for biological applications. However, its conformational flexibility limits its utilization as protein ligands. Recently, the introduction of backbone substituents to oligo-NSG has been demonstrated to restrict its own backbone bond rotations via steric interactions, and the resulting oligo(N-substituted alanine) (oligo-NSA) has been demonstrated to be a conformationally constrained oligomer. Here, we review the concept, history, synthetic methodologies, conformational analysis, and biological applications of the new synthetic oligomer. We also conducted overview research on N-substituted peptides consisting of non-a-amino acid residues to facilitate the plausible future expansion of the conformationally constrained peptoids of diverse three-dimensional structures.