Issue 23, 2020

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

Abstract

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 macrocyclic host. Here we show that cucurbit[7]uril binding with N-terminal phenylalanine significantly reduces the nucleophilicity 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.

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

Supplementary files

Article information

Article type
Communication
Submitted
02 Dzi 2020
Accepted
19 Mud 2020
First published
27 Mud 2020

Org. Biomol. Chem., 2020,18, 4371-4375

Author version available

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

A. A. A. Smith, C. L. Maikawa, G. A. Roth and E. A. Appel, Org. Biomol. Chem., 2020, 18, 4371 DOI: 10.1039/D0OB01004A

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