foldamerssynthetic

Foldamers are synthetic oligomers engineered to fold into well-defined three-dimensional structures, emulating certain aspects of natural biopolymers in architecture and function. The field explores non-natural backbones that promote intramolecular folding through hydrogen bonding, steric constraints, and hydrophobic interactions, aiming for predictable shapes with potential biological or material relevance.

Common classes include beta-peptides and alpha/beta-peptides, peptoids (N-substituted glycine oligomers), and aromatic foldamers. Each class favors different folding motifs, such as helices or sheet-like structures, allowing rational control over geometry and surface functionality. Synthesis is usually performed by solid-phase methods, enabling rapid assembly of diverse sequences and backbones, sometimes complemented by macromolecular templates or ring-closing strategies.

Characterization employs circular dichroism, NMR spectroscopy, X-ray crystallography, and computational modeling to assess folding propensity, thermodynamic stability, and structural fidelity. Applications span drug discovery, where foldamers act as receptor mimics or inhibitors; catalysis, as artificial enzymes; and materials science, where defined shapes enable novel assemblies and functions. Although foldamers can offer enhanced proteolytic stability and tunable rigidity, challenges include achieving long-range predictable folding across larger systems and scalable synthesis for complex backbones.