Foldamers: design principles, building blocks and applications

Abstract

This review article explores foldamers, a class of synthetic oligomers designed to mimic the structural and functional diversity of natural proteins. We begin by defining foldamers and outlining their significance, tracing the historical development of the field and highlighting key milestones that shaped its progress. The article examines the fundamental design principles of foldamers. Particular attention is given to backbone building blocks, the intra- and intermolecular interactions that stabilise folded structures, and the influence of side-chain functionality and stereochemistry. The growing contribution of computational methods in predicting foldamer conformations and dynamics is also addressed. A central part of this review is devoted to structural diversity, guiding the reader through foldamer architectures ranging from phenylene–ethynylene and aryltriazole systems to oligoamides, oligoureas, indolocarbazoles, and other notable scaffolds. This structural journey sets the stage for a survey of applications, which include foldamer-based anion receptors and transporters, cation sensors, biomolecular recognition capsules, and systems for protein complex and surface recognition. We also highlight developments in foldamer-based stimuli-responsive materials and other emerging applications.