دورية أكاديمية

Development of a target identification approach using native mass spectrometry

التفاصيل البيبلوغرافية
العنوان: Development of a target identification approach using native mass spectrometry
المؤلفون: Miaomiao Liu, Wesley C. Van Voorhis, Ronald J. Quinn
المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
بيانات النشر: Nature Portfolio, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract A key step in the development of new pharmaceutical drugs is the identification of the molecular target and distinguishing this from all other gene products that respond indirectly to the drug. Target identification remains a crucial process and a current bottleneck for advancing hits through the discovery pipeline. Here we report a method, that takes advantage of the specific detection of protein–ligand complexes by native mass spectrometry (MS) to probe the protein partner of a ligand in an untargeted method. The key advantage is that it uses unmodified small molecules for binding and, thereby, it does not require labelled ligands and is not limited by the chemistry required to tag the molecule. We demonstrate the use of native MS to identify known ligand–protein interactions in a protein mixture under various experimental conditions. A protein–ligand complex was successfully detected between parthenolide and thioredoxin (PfTrx) in a five-protein mixture, as well as when parthenolide was mixed in a bacterial cell lysate spiked with PfTrx. We provide preliminary data that native MS could be used to identify binding targets for any small molecule.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-021-81859-4
URL الوصول: https://doaj.org/article/79735f1a181546f9a030b3da081e8bf6
رقم الأكسشن: edsdoj.79735f1a181546f9a030b3da081e8bf6
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-021-81859-4