English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Critical Evaluation of Native Electrospray Ionization Mass Spectrometry for Fragment-Based Screening

MPS-Authors
/persons/resource/persons104330

Göth,  Melanie
Institute of Chemistry and Biochemistry Freie Universität Berlin;
Molecular Physics, Fritz Haber Institute, Max Planck Society;

/persons/resource/persons32738

Pagel,  Kevin
Institute of Chemistry and Biochemistry Freie Universität Berlin;
Molecular Physics, Fritz Haber Institute, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Göth, M., Badock, V., Weiske, J., Pagel, K., & Kuropka, B. (2017). Critical Evaluation of Native Electrospray Ionization Mass Spectrometry for Fragment-Based Screening. ChemMedChem. doi:10.1002/cmdc.201700177.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-98FA-D
Abstract
Fragment-based screening presents a promising alternative to high-throughput screening and has gained great attention over the last years. So far, only a few studies discuss mass spectrometry as a screening technology for fragments. Here, we applied native electrospray ionization mass spectrometry (ESI-MS) for screening defined sets of fragments against four different target proteins. Fragments were selected from a primary screen conducted by thermal shift assay (TSA) and represent different binding categories. Our data show that beside specific complex formation, many fragments show extensive multiple binding as well as charge-state shifts. Both of these factors complicate automated data analysis and lower the attractiveness of native MS as a primary screening tool for fragments. A comparison of hits identified by native MS and TSA shows good agreement for two proteins. Furthermore, we discuss general obstacles including the determination of an optimal fragment concentration and the question of how to rank fragment hits according to their affinity. In conclusion, we consider native MS a highly valuable tool for the validation and deeper investigation of promising fragment hits rather than a method for primary screening.