ArticleCell chemical biology2024
An N terminomics toolbox combining 2-pyridinecarboxaldehyde probes and click chemistry for profiling protease specificity.
Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- N-Terminal protein sequencing by nicotinic acid derivatization and MS analysis.Analytical and bioanalytical chemistry · 2026Article
- Degradomics for large-scale mechanistic insights on proteases and proteolysis in human health.The FEBS journal · 2026Review
- Phosphoproteome-derived peptide libraries for deep specificity profiling of phosphatases and phospholyases.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proteolysis activity mapping and substrate discovery platform for identifying tumor-activated biosensors.Nature chemical biology · 2026Article
- Pyrene-Conjugated, 2-Pyridinecarboxaldehyde Derivatives as N-Terminus-Specific Tags for MALDI- and LALDI-MS.Rapid communications in mass spectrometry : RCM · 2026Article
- Exploiting Selective Position Labeling to Unveil the Hidden Complexity of Terminomics.Molecules (Basel, Switzerland) · 2026Review
- Unraveling the Conformational and Electronic Landscape of 3‑Pyridinecarboxaldehyde: A Spectroscopic Journey through Conformer-Specific Ionization.ACS physical chemistry Au · 2025Article
- Data Processing and Analysis in Positional Proteomics.Proteomics · 2025Review
- Four guidelines to identify bona fide protease-substrate pairs.Journal of experimental botany · 2025Review
- Employing complementary fractionation-based N-terminomics approaches enhances the identification of legumain cleavage events in naïve and inflamed colon tissue.Protein science : a publication of the Protein Society · 2025Article
- Ten "Cheat Codes" for Measuring Oxidative Stress in Humans.Antioxidants (Basel, Switzerland) · 2024Review
- CLIPPER 2.0: Peptide-Level Annotation and Data Analysis for Positional Proteomics.Molecular & cellular proteomics : MCP · 2024Article
- Functionalizing tandem mass tags for streamlining click-based quantitative chemoproteomics.Communications chemistry · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Proteomic profiling of protease-generated N termini provides key insights into protease function and specificity. However, current technologies have sequence limitations or require specialized synthetic reagents for N-terminal peptide isolation. Here, we introduce an N terminomics toolbox that combines selective N-terminal biotinylation using 2-pyridinecarboxaldehyde (2PCA) reagents with chemically cleavable linkers to enable efficient enrichment of protein N termini. By incorporating a commercially available alkyne-modified 2PCA in combination with Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), our strategy eliminates the need for chemical synthesis of N-terminal probes. Using these reagents, we developed PICS2 (Proteomic Identification of Cleavage Sites with 2PCA) to profile the specificity of subtilisin/kexin-type proprotein convertases (PCSKs). We also implemented CHOPPER (chemical enrichment of protease substrates with purchasable, elutable reagents) for global sequencing of apoptotic proteolytic cleavage sites. Based on their broad applicability and ease of implementation, PICS2 and CHOPPER are useful tools that will advance our understanding of protease biology.
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