ArticleCell chemical biology2021
Native mass spectrometry and gas-phase fragmentation provide rapid and in-depth topological characterization of a PROTAC ternary complex.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Native Mass Spectrometry Analysis of Cullin-RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.Analytical chemistry · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Interface Architecture of a VHL-PROTAC Complex with and without Cullin-2.Journal of the American Chemical Society · 2026Article
- Unveiling BCL-xL-specific PROTAC efficiency and dissociation pathways using native mass spectrometry.Chemical science · 2026Article
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Native Mass Spectrometry Analysis of Cullin RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Hydrogen-Deuterium Exchange Mass Spectrometry for Molecular Glue Characterization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rational Design of a Foldon-Derived Heterotrimer Guided by Quantitative Native Mass Spectrometry.Journal of the American Chemical Society · 2025Article
- Traversing the drug discovery landscape using native mass spectrometry.Current opinion in structural biology · 2025Review
- Mechanism of degrader-targeted protein ubiquitinability.Science advances · 2024Article
- Targeted protein degradation in CNS disorders: a promising route to novel therapeutics?Frontiers in molecular neuroscience · 2024Review
- The Time and Place for Nature in Drug Discovery.JACS Au · 2022Review
- Recent technological developments for native mass spectrometry.Biochimica et biophysica acta. Proteins and proteomics · 2022Review
- Estimating the cooperativity of PROTAC-induced ternary complexes usingRSC medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Proteolysis-targeting chimeras (PROTACs) represent a new direction in small-molecule therapeutics whereby a heterobifunctional linker to a protein of interest (POI) induces its ubiquitination-based proteolysis by recruiting an E3 ligase. Here, we show that charge reduction, native mass spectrometry, and gas-phase activation methods combine for an in-depth analysis of a PROTAC-linked ternary complex. Electron capture dissociation (ECD) of the intact POI-PROTAC-VCB complex (a trimeric subunit of an E3 ubiquitin ligase) promotes POI dissociation. Collision-induced dissociation (CID) causes elimination of the nonperipheral PROTAC, producing an intact VCB-POI complex not seen in solution but consistent with PROTAC-induced protein-protein interactions. In addition, we used ion mobility spectrometry (IMS) and collisional activation to identify the source of this unexpected dissociation. Together, the evidence shows that this integrated approach can be used to screen for ternary complex formation and PROTAC-protein contacts and may report on PROTAC-induced protein-protein interactions, a characteristic correlated with PROTAC selectivity and efficacy.
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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.