Site-selective modification of proteins using cucurbit[7]uril as supramolecular protection for N-terminal aromatic amino acids

摘要

Cucurbit[7,8]urils are known to form inclusion complexes with aromatic amino acids, hosting the hydrohobic side chains within the cavity and adjacent cations within the portal of the macro-cyclic host. Here we show that cucurbit[7]uril binding with N-terminal phenylalanine significantly reduces the nucleophiticity of the amine, likely due to an increase in stability of the ammonium ion, rendering it unreactive at neutral pH. Using insulin as a model protein, we show that this supramolecular protection strategy can drive selectivity of N-terminal amine conjugation away from the preferred B chain N-terminal phenylalanine towards the A chain N-terminal glycine. Cucurbit[7]uril can therefore be used as a supramolecular protecting group for site-selective protein modification.