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Supramolecular chemistry based on macrocycles such as cyclodextrins (CDs) offers the opportunity to combine synthetic motifs with naturally occurring macromolecules for the study of biological phenomena. CDs, a family of cone-shaped cyclic oligosaccharides, can selectively encapsulate various organic and inorganic molecules in their hydrophobic cavities (host–guest interactions), thereby generating reproducible, well-defined biological nanostructures with novel functionalities and environmental adaptability. In this chapter, we highlight recent work on strategies used to design and construct a diverse array of biocompatible CD-protein nanoassemblies of varying complexity. The binding characteristics of CD-based inclusion complexes are described, the responses of the complexes to chemical and physical stimuli are summarized, the principles used to design CD-based enzyme and protein mimics are discussed, and strategies for fabrication of CD-protein constructs are reviewed, with a particular focus on orthogonal host–guest complexation and ligand–receptor interactions. Such CD-protein constructs can be expected not only to allow precise manipulation of protein–protein interactions but also to provide a wealth of information about the dynamic self-assembly of biomacromolecules, which can pave the way for the development of intelligent bioinspired nanomaterials with functions that closely resemble those of naturally occurring biological materials.

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