Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes
| العنوان: | Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes |
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| المؤلفون: | Nathanael S. Gray, Michael J. Eck, Randall McNally, Tinghu Zhang, Hyuk-Soo Seo, Jarrod A. Marto, William M. Alexander, Christopher M. Browne, Ilaria Lamberto, Sirano Dhe-Paganon, Eun Young Park, Joseph D. Card, Sara J. Buhrlage, Scott B. Ficarro |
| المصدر: | Analytical Chemistry. 88:12248-12254 |
| بيانات النشر: | American Chemical Society (ACS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Proteomics, 0301 basic medicine, Mass spectrometry, Dissociation (chemistry), Analytical Chemistry, Gas phase, 03 medical and health sciences, chemistry.chemical_compound, Piperidines, Fragmentation (mass spectrometry), Tandem Mass Spectrometry, Cell Line, Tumor, Drug Discovery, medicine, Humans, Amino Acid Sequence, Molecular Targeted Therapy, Protein Kinase Inhibitors, Peptide sequence, Chemistry, Adenine, Combinatorial chemistry, Pyrimidines, 030104 developmental biology, Covalent bond, Ibrutinib, Neratinib, Quinolines, Pyrazoles, Peptides, Protein Kinases, medicine.drug |
| الوصف: | The recent approval of covalent inhibitors for multiple clinical indications has reignited enthusiasm for this class of drugs. As interest in covalent drugs has increased, so too has the need for analytical platforms that can leverage their mechanism-of-action to characterize modified protein targets. Here we describe novel gas phase dissociation pathways which yield predictable fragment ions during MS/MS of inhibitor-modified peptides. We find that these dissociation pathways are common to numerous cysteine-directed probes as well as the covalent drugs, Ibrutinib and Neratinib. We leverage the predictable nature of these fragment ions to improve the confidence of peptide sequence assignment in proteomic analyses and explore their potential use in selective mass spectrometry-based assays. |
| تدمد: | 1520-6882 0003-2700 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a8c5497903772fb38883f16ea5f7e44 https://doi.org/10.1021/acs.analchem.6b03394 |
| رقم الأكسشن: | edsair.doi.dedup.....7a8c5497903772fb38883f16ea5f7e44 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15206882 00032700 |
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