Structural Studies Using Unnatural Oligosaccharides: Toward Sugar Foldamers

Biopolymers, like DNA and proteins, fold in specific conformations in order to exert complex biological functions. Synthetic modifications are commonly used to alter those conformations and create engineered biomaterials. In stark contrast, the chemical complexity and dynamic nature of polysaccharides have hampered a detailed structural characterization and structure–function correlations are still incomplete. Many synthetic strategies have been developed to access complex unnatural oligosaccharides, capable of mimicking or even improving the properties of the natural counterpart. However, the structural features behind these results are often neglected. This perspective highlights the approaches adopted to develop unnatural glycans, with a particular focus on how the insertion of specific modifications results in more flexible or more constrained structures. Synthetic analogues of natural oligosaccharides could shine light on fundamental structural features. The combination of modern synthetic, computati...