New covalent bonding ability for proteins

• Published in: Protein science Vol. 31; no. 2; pp. 312 - 322
• Main Authors: Cao, Li, Wang, Lei
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2022; Wiley Subscription Services, Inc
• Subjects: Amino acids; Amino Acids - chemistry; Bonding; Chemical bonds; Covalence; Covalent bonds; covalent drug; Genetic code; genetic code expansion; latent bioreactive unnatural amino acid; Ligands; Protein Binding; Protein Engineering; Protein interaction; protein therapeutics; Proteins; Proteins - chemistry; protein–protein interaction; proximity‐enabled bioreactivity; Review; latent bioreactive unnatural amino acid; genetic code expansion; protein-protein interaction; protein therapeutics; proximity-enabled bioreactivity; covalent drug
• ISSN: 0961-8368; 1469-896X; 1469-896X
• DOI: 10.1002/pro.4228

To expand protein's covalent bonding ability, latent bioreactive unnatural amino acids have been designed and genetically encoded into proteins, which react with specific natural amino acid residues through proximity‐enabled bioreactivity. The resultant new covalent bonds can be selectively created within and between proteins in vitro, in cells, and in vivo. Offering diverse properties previously unattainable, these covalent linkages have been harnessed to enhance protein properties, to modulate protein function, to probe ligand–receptor binding, to identify elusive protein interactions, and to develop covalent protein drugs. Selective introduction of covalent bonds into proteins is affording novel avenues for biological studies, synthetic biology, and biotherapeutics.