Advancing In-Depth N-Terminomics Detection with a Cleavable 2-Pyridinecarboxyaldehyde Probe.

J Am Chem Soc

State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Published: March 2024


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Article Abstract

Proteolysis, an irreversible post-translational modification catalyzed by proteases, plays a crucial role in various biological processes. Exploring abnormally hydrolyzed proteins in pathological tissues is a valuable approach for elucidating the mechanisms underlying disease development. Herein, we have developed a cleavable 2-pyridinecarboxyaldehyde probe (2PCA-Probe) that enables efficient and in-depth N-terminomics detection, addressing limitations of previous methods. Furthermore, we unexpectedly discovered a new marker capable of identifying N-terminal chemical labeling with the 2PCA-Probe and elucidated the reaction mechanism. Using this probe, we identified 4686 N-terminal peptides in colorectal cancer and adjacent tissues, significantly expanding the depth of the N-terminome and revealing the potential role of abnormal protein hydrolysis in colorectal cancer development.

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