ArticleAnalytical chemistry2022
Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation.
Article in Analytical chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Photosensitizer proximity labeling captures the lipid and protein interactomes.Nature chemical biology · 2026Article
- Small-molecule binding-site discovery using silyl ether-enabled chemoproteomics.Nature chemistry · 2026Article
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- Navigating Challenges in Mass Spectrometry Analysis of Endogenous and Synthetic Protein Modifications.Biomolecules · 2026Review
- One-step labeling with a fluorinated porphyrin-based probe enablesInnovation (Cambridge (Mass.)) · 2025Article
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- Gas Phase Separation of Modified Peptides for Activity-Based Protein Profiling.Analytical chemistry · 2025Article
- CIAA: Integrated Proteomics and Structural Modeling for Understanding Cysteine Reactivity with Iodoacetamide Alkyne.ACS chemical biology · 2025Article
- Acid Cleavable Biotin-Alkyne Improves Sensitivity for Direct Detection of Biotin Labeled Peptides in Biorthogonal Noncanonical Amino Acid Tagging Analysis.Journal of proteome research · 2024Article
- Chemical proteomic mapping of reversible small molecule binding sites in native systems.Trends in pharmacological sciences · 2024Review
- Chemoproteogenomic stratification of the missense variant cysteinome.Nature communications · 2024Article
- Investigation and Development of the BODIPY-Embedded Isotopic Signature for Chemoproteomics Labeling and Targeted Profiling.Journal of the American Society for Mass Spectrometry · 2024Article
- Functionalizing tandem mass tags for streamlining click-based quantitative chemoproteomics.Communications chemistry · 2024Article
- Improved deconvolution of natural products' protein targets using diagnostic ions from chemical proteomics linkers.Beilstein journal of organic chemistry · 2024Review
- Article
- Defining the Cell Surface Cysteinome using Two-step Enrichment Proteomics.bioRxiv : the preprint server for biology · 2023Article
- Solid-Phase Compatible Silane-Based Cleavable Linker Enables Custom Isobaric Quantitative Chemoproteomics.Journal of the American Chemical Society · 2023Article
- Multi-omic stratification of the missense variant cysteinome.bioRxiv : the preprint server for biology · 2023Article
- Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.Cell chemical biology · 2023Article
- Detecting diagnostic features in MS/MS spectra of post-translationally modified peptides.Nature communications · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mass spectrometry-based chemoproteomics has enabled functional analysis and small molecule screening at thousands of cysteine residues in parallel. Widely adopted chemoproteomic sample preparation workflows rely on the use of pan cysteine-reactive probes such as iodoacetamide alkyne combined with biotinylation via copper-catalyzed azide-alkyne cycloaddition (CuAAC) or "click chemistry" for cysteine capture. Despite considerable advances in both sample preparation and analytical platforms, current techniques only sample a small fraction of all cysteines encoded in the human proteome. Extending the recently introduced labile mode of the MSFragger search engine, here we report an in-depth analysis of cysteine biotinylation via click chemistry (CBCC) reagent gas-phase fragmentation during MS/MS analysis. We find that CBCC conjugates produce both known and novel diagnostic fragments and peptide remainder ions. Among these species, we identified a candidate signature ion for CBCC peptides, the cyclic oxonium-biotin fragment ion that is generated upon fragmentation of the N(triazole)-C(alkyl) bond. Guided by our empirical comparison of fragmentation patterns of six CBCC reagent combinations, we achieved enhanced coverage of cysteine-labeled peptides. Implementation of labile searches afforded unique PSMs and provides a roadmap for the utility of such searches in enhancing chemoproteomic peptide coverage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.