A macropolycyclic catalyst, cucurbit [8]uril can induce proximitydriven Michael addition through the assembly of a tryptophan residue and bipyridinium derivative (Scheme 16B). Cucurbituril is a macropolycyclic compound assembled from glycoluril and formaldehyde. Cucurbituril acts as a host molecule for various guests such as hydrocarbons, saccharides, dyes, amino acids, and proteins through hydrophobic interactions, ion-dipole interactions, and dipole-dipole interactions. Through such supramolecular capability, cucurbituril-mediated chemistry has been employed for protein modification such as azide-alkyne cycloaddition reactions enhanced through the hydrogen bonding network. For modification of proteins with natural amino acid side chains, cucurbit [8]uril-a cucurbituril that contains eight glycoluril units-was used for supramolecular catalysis-based Michael addition reaction modifying a cysteine residue through inclusion of both a bipyridinium group on the labeling reagent and a tryptophan residue simultaneously. Through this approach, cucurbit [8]uril-facilitated modification of a KRas protein was achieved using dehydroalanine-bipyridinium reagent; cucurbit [8]uril served as a host to a tryptophan residue of KRas and bipyridinium for labeling, followed by a proximity-induced thia-Michael reaction between cysteine residue on the substrate and dehydroalanine on the labeling reagent. It should be also noted that supramolecular catalysis-based chemical backbone hydrolysis has been also achieved using a polymacrocyclic catalyst, although their substrate scope is limited to peptides. 197