CHAPTER 4: Protein Modulation by Cucurbiturils

Cucurbiturils are a class of macrocycles that feature highly interesting molecular characteristics that enable interfacing with proteins. These macrocycles, of different ring sizes, can act as host molecules to form stable inclusion complexes with various protein elements as guests. This combination of diverse macrocycle ring sizes with the large variety of protein elements, ranging from individual amino acids to protein segments, has provided a wealth of opportunities to bring cucurbiturils to applications in protein modulation. Cucurbit[6]uril, cucurbit[7]uril, and cucurbit[8]uril are the most prominent examples with applications in protein binding, as their chemical characteristics appear to be ideally suited to recognize different protein epitopes with high affinity. This interplay has allowed these cucurbiturils to be used for protein binding with concomitant functional modulation, which includes the study and modulation of protein activity and protein assembly. This chapter will provide an overview of the amino acid, peptide and protein recognition as well as protein modulatory activities of cucurbit[6]uril, cucurbit[7]uril, and cucurbit[8]uril. Specific examples will illustrate the broader potential for molecular recognition of proteins by cucurbiturils.