Issue 3, 2023

Chemical modification of proteins – challenges and trends at the start of the 2020s

Abstract

Ribosomally expressed proteins perform multiple, versatile, and specialized tasks throughout Nature. In modern times, chemically modified proteins, including improved hormones, enzymes, and antibody–drug-conjugates have become available and have found advanced industrial and pharmaceutical applications. Chemical modification of proteins is used to introduce new functionalities, improve stability or drugability. Undertaking chemical reactions with proteins without compromising their native function is still a core challenge as proteins are large conformation dependent multifunctional molecules. Methods for functionalization ideally should be chemo-selective, site-selective, and undertaken under biocompatible conditions in aqueous buffer to prevent denaturation of the protein. Here the present challenges in the field are discussed and methods for modification of the 20 encoded amino acids as well as the N-/C-termini and protein backbone are presented. For each amino acid, common and traditional modification methods are presented first, followed by more recent ones.

Graphical abstract: Chemical modification of proteins – challenges and trends at the start of the 2020s

Article information

Article type
Review Article
Submitted
05 Aug 2022
Accepted
27 Nov 2022
First published
28 Nov 2022

Biomater. Sci., 2023,11, 719-748

Chemical modification of proteins – challenges and trends at the start of the 2020s

N. H. Fischer, M. T. Oliveira and F. Diness, Biomater. Sci., 2023, 11, 719 DOI: 10.1039/D2BM01237E

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