Photocatalytic Modification of Amino Acids, Peptides, and Proteins

Abstract

In the last decade, visible-light photoredox catalysis has emerged as a powerful strategy to enable novel transformations in organic synthesis. Owing to mild reaction conditions (i.e., room temperature, use of visible light) and high functional-group tolerance, photoredox catalysis could represent an ideal strategy for chemoselective biomolecule modification. Indeed, a recent trend in photoredox catalysis is its application to the development of novel methodologies for amino acid modification. Herein, an up-to-date overview of photocatalytic methodologies for the modification of single amino acids, peptides, and proteins is provided. The advantages offered by photoredox catalysis and its suitability in the development of novel biocompatible methodologies are described. In addition, a brief consideration of the current limitations of photocatalytic approaches, as well as future challenges to be addressed, are discussed.

Photocatalytic Proximity Labelling of MCL-1 by a BH3 Ligand

“…More importantly, Ru(II)(bpy)3 and related complexes have been used for the formation of thiol radicals and their use in C-S bond formation, including on peptides. [52][53][54] In addition, the group of Finn demonstrated the use of Ru(II)(bpy)3-mediated photolabelling of Tyr residues of viral capsid proteins with thiol derivatives, 55 suggesting that thiols can efficiently form C-S bonds with electron-rich aromatics in these types of reactions. It should be noted that the distance limits of SETmediated protein labelling (and therefore residue selectivity) may depend on the contribution of different reaction pathways, which in turn may depend on the type of RTA used.…”

Versatile Ru‐Photoredox‐Catalyzed Functionalization of Dehydro‐Amino Acids and Peptides

“…In this regard, visible‐light photoredox catalysis has recently emerged as a powerful strategy for the activation of organic molecules under mild conditions, while enabling unprecedented transformations . Indeed, due to its mildness, photocatalysis presents an intrinsic large functional group tolerance, being compatible with highly functionalized compounds such as amino acids or peptides . Based on this, several procedures for the photocatalytic modification of amino acid derivatives have been recently developed.…”

“…[3] Indeed, due to its mildness, photo-catalysis presents an intrinsic large functional group tolerance, being compatible with highly functionalized compounds such as amino acids or peptides. [4] Based on this, several procedures for the photocatalytic modification of amino acid derivatives have been recently developed. Besides the derivatization of functional groups of amino acid residues such as sulfurcontaining cysteine [5] and methionine [6] or aromatic rests such as in tyrosine [7] and tryptophan, [8] an interesting alternative approach is based on decarboxylative couplings (Scheme 1a).…”

Photoredox‐Mediated Hydrogen Isotope Exchange Reactions of Amino‐Acids, Peptides, and Peptide‐Derived Drugs

“…Furthermore, as most peptides are prone to degradation at elevated temperatures, photochemistry appeared to us as great tool for developing ac onvenient methodf or their deuteration and tritiation, due to the mild reaction conditions required. [17] Results and Discussion…”