ArticleNature communications2023
N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 28 citations in OpenAlex.
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- Illuminating the Druggable Human Proteome with an AI Protein Profiling Platform.Research square · 2025Article
- Illuminating the Druggable Human Proteome with an AI Protein Profiling Platform.bioRxiv : the preprint server for biology · 2025Article
- Proteome-wide ligandability maps of drugs with diverse cysteine-reactive chemotypes.Nature communications · 2025Article
- Protein Electrostatic Properties are Fine-Tuned Through Evolution.Research square · 2025Article
- Activity-Based Protein Profiling for Functional Cysteines and Protein Target Identification.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Superoxide-responsive quinone methide precursors (QMP-SOs) to study superoxide biology by proximity labeling and chemoproteomics.RSC chemical biology · 2024Article
- Chemoproteomic capture of RNA binding activity in living cells.Nature communications · 2023Article
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4 authors at 2 institutions in 3 countries.
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Abstract
Cysteine has been exploited as the binding site of covalent drugs. Its high sensitivity to oxidation is also important for regulating cellular processes. To identify new ligandable cysteines which can be hotspots for therapy and to better study cysteine oxidations, we develop cysteine-reactive probes, N-acryloylindole-alkynes (NAIAs), which have superior cysteine reactivity owing to delocalization of π electrons of the acrylamide warhead over the whole indole scaffold. This allows NAIAs to probe functional cysteines more effectively than conventional iodoacetamide-alkyne, and to image oxidized thiols by confocal fluorescence microscopy. In mass spectrometry experiments, NAIAs successfully capture new oxidized cysteines, as well as a new pool of ligandable cysteines and proteins. Competitive activity-based protein profiling experiments further demonstrate the ability of NAIA to discover lead compounds targeting these cysteines and proteins. We show the development of NAIAs with activated acrylamide for advancing proteome-wide profiling and imaging ligandable cysteines and oxidized thiols.
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