Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

Lysine monomethylation (Kme) is an impactful post‐translational modification (PTM) responsible for regulating biological processes and implicated in diseases, thus there is great interest in identifying these methylation marks globally. However, the progress in this area has been challenging because...

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Bibliographic Details
Published in:Angewandte Chemie 2021-03, Vol.133 (13), p.7420-7428
Main Authors: Nwajiobi, Ogonna, Mahesh, Sriram, Streety, Xavier, Raj, Monika
Format: Article
Language:English
Subjects:
Amines
Biocompatibility
bioconjugation
Biological activity
Chemical technology
Chemistry
chemoselectivity
Decoupling
Hydrophobicity
Lysine
Marking
Methylation
monomethyl lysine
Peptides
protein modifications
proteomics
Salts
Translation
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Summary:Lysine monomethylation (Kme) is an impactful post‐translational modification (PTM) responsible for regulating biological processes and implicated in diseases, thus there is great interest in identifying these methylation marks globally. However, the progress in this area has been challenging because the addition of a small methyl group on lysine leads to negligible change in the bulk, charge, and hydrophobicity. Herein, we report an empowering chemical technology selective triazenation reaction, which we term “STaR”, of secondary amines using arene diazonium salts to achieve highly selective, rapid, and robust tagging of Kme peptides from a complex mixture under biocompatible conditions. Although the resulting triazene‐linkage with Kme is stable, we highlight the efficient decoupling of the triazene‐conjugate to afford unmodified starting components under mild conditions when desired. Our work establishes a unique chemoselective, traceless bioconjugation strategy for the selective enrichment of Kme PTMs. We report a novel chemoselective selective triazenation reaction, termed „STaR“, of secondary amines for the selective enrichment of monomethyl lysine (Kme) post‐translational modifications from a complex protein mixture using diazonium ions under physiological conditions followed by the „traceless“ release of the Kme peptides under mild acidic conditions.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202013997