TY - JOUR

T1 - Chemical modification of proteins - challenges and trends at the start of the 2020s

AU - Fischer, Niklas Henrik

AU - Oliveira, Maria Teresa

AU - Diness, Frederik

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - EXTRINSIC CROSS-LINK

KW - SELECTIVE BIOCONJUGATION

KW - RIBONUCLEASE-A

KW - DUAL FUNCTIONALIZATION

KW - REDUCTIVE ALKYLATION

KW - HISTIDINE-RESIDUES

KW - N-ETHYLMALEIMIDE

KW - FOLDING PATHWAY

KW - CLICK LIGATION

KW - AMINO-GROUPS

U2 - 10.1039/d2bm01237e

DO - 10.1039/d2bm01237e

M3 - Review

C2 - 36519403

VL - 11

SP - 719

EP - 748

JO - Biomaterials Science

JF - Biomaterials Science

SN - 2047-4830

IS - 3

ER -