Work

Precision Chemistry for Protein Lysine Modification

Year: 2026

Type: article

Abstract: Lysine post-translational modifications (PTMs) play crucial roles in regulating protein structures, interactions, and cellular signaling. Precise study of PTM functions requires homogeneous proteins with modifications at defined sites; however, selective chemical modification is challenging because multiple lysines undergo similar chemistry yet exhibit variable reactivity depending on their local environments. Early chemical strategies exploited intrinsic reactivity differences, which are effective for exposed lysines but limited for low-reactivity or sterically hindered sites. In contrast, enzymes achieve high selectivity through substrate recognition and spatial organization. Inspired by this enzymatic principle, chemical approaches have been developed, including ligand-directed chemistry, proximity-enabled modification, and on-demand generation of highly reactive electrophiles. Recent advances in ligand-guided catalysis now enable regioselective and catalytic installation of biorelevant, authentic PTMs, providing a platform for programmable lysine modification and synthetic epigenetics.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.71193

Authors: Mayu Onoda, Motomu Kanai

Institution: The University of Tokyo

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,640

Funders: Japan Society for the Promotion of Science, Japan Science and Technology Agency, Core Research for Evolutional Science and Technology