Foldamerbased

Foldamer-based materials refer to systems constructed from foldamers—synthetic oligomers designed to adopt stable, non-native secondary structures that mimic protein folding. Foldamers include beta- and gamma-peptides, peptoids, and aromatic backbones that fold into helices, sheets, or other shapes in solution or solid state. By constraining sequence and backbone, foldamer-based designs achieve predictable three-dimensional structures that can serve as functional scaffolds for molecular recognition, catalysis, or material assembly.

Design and chemistry: Folding is stabilized by intramolecular hydrogen bonds, stacking interactions, and steric constraints. Different backbones favor different motifs (e.g., helices in beta-peptides). Synthesis is often via solid-phase synthesis or solution methods, with careful protection schemes; computational design aids in selecting monomer sequences and backbones to promote desired folds.

Applications: In drug discovery, foldamer-based ligands can bind protein targets with high affinity and selectivity, often displaying enhanced stability versus natural peptides. In materials science, foldamer-based building blocks enable self-assembly into nanotubes, fibers, or porous frameworks, as well as catalysts with defined pockets. In sensing, foldamers offer selective recognition of ions, small molecules, or biomolecules.

Challenges and outlook: Key challenges include synthesis cost and complexity, limited library sizes, and the need for robust structure–function data in diverse environments. Ongoing research aims to expand monomer chemistries, improve scalability, and integrate foldamers into hybrid materials with dynamic properties.