2024/11/07 by Kacper Skakuj, Maximilian Iglhaut, Qian Shao +7 · 1 voice · 5 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · Neuroscience · #Amino acid #Biochemistry #Chemistry #Medicine #Photoreceptor and optogenetics research #Radical Photochemical Reactions #Reactivity (psychology) #bioluminescence and chemiluminescence research
paper · pdf · doi:10.1002/anie.202415976
published in Angewandte Chemie International Edition 64(4), e202415976 (Wiley)
openalex publication_date 2024/11/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Controlled modifications of amino acids are an indispensable tool for advancing fundamental and translational research based on peptides and proteins. Yet, we still lack methods to chemically modify each naturally occurring amino acid sidechain. To help address this gap, we show that N,α-diaryl oxaziridines expand the scope of bioconjugation methods to chemically modify cysteine, methionine, and tryptophan residues with evidence for additional tyrosine labelling in a proteomic context. Conjugation primarily at tryptophan sites can be accessed by selective cleavage of modifications at other sidechains. The N,α-diaryl oxaziridine reagents are accessed through photoisomerization of nitrones, which serve as photocaged reagents, thus providing an additional level of control over reactivity. Initial guiding principles for the design of nitrone reagents are developed by exploring the impact of structure on UV/Vis absorption, photoisomerization, and reactivity. We identify a nitrone structure that maximizes photoisomerization efficiency, the aqueous stability of the oxaziridine, the extent of amino acid modification, and the stability of the resulting amino acid conjugates. We then translate nitrone reagents to modify proteins in aqueous conditions. Finally, we use nitrones to profile reactive residues across the proteome of a mammalian cell line and find that they expand the proteome coverage.