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Nanoscale Ion Emitters in Native Mass Spectrometry for Measuring Ligand-Protein Binding Affinities

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اقرأ أكثر حفظ في قائمتي
  • المؤلفون: Nguyen, Giang T H; Tran, Thinh N; Podgorski, Matthew N; Bell, Stephen G; Supuran, Claudiu T; Donald, William A
  • المصدر:
    Nguyen, Giang T H; Tran, Thinh N; Podgorski, Matthew N; Bell, Stephen G; Supuran, Claudiu T; Donald, William A (2019). Nanoscale Ion Emitters in Native Mass Spectrometry for Measuring Ligand-Protein Binding Affinities. ACS Central Science, 5(2):308-318.
  • نوع التسجيلة:
    Electronic Resource
  • الدخول الالكتروني :
    https://www.zora.uzh.ch/id/eprint/183850/
    https://www.zora.uzh.ch/id/eprint/183850
    10.1021/acscentsci.8b00787
  • معلومة اضافية
    • Publisher Information:
      American Chemical Society (ACS) 2019-02-27
    • نبذة مختصرة :
      Electrospray ionization (ESI) mass spectrometry (MS) is a crucial method for rapidly determining the interactions between small molecules and proteins with ultrahigh sensitivity. However, nonvolatile molecules and salts that are often necessary to stabilize the native structures of protein-ligand complexes can readily adduct to protein ions, broaden spectral peaks, and lower signal-to-noise ratios in native MS. ESI emitters with narrow tip diameters (∼250 nm) were used to significantly reduce the extent of adduction of salt and nonvolatile molecules to protein complexes to more accurately measure ligand-protein binding constants than by use of conventional larger-bore emitters under these conditions. As a result of decreased salt adduction, peaks corresponding to protein-ligand complexes that differ in relative molecular weight by as low as 0.06% can be readily resolved. For low-molecular-weight anion ligands formed from sodium salts, anion-bound and unbound protein ions that differ in relative mass by 0.2% were completely baseline resolved using nanoscale emitters, which was not possible under these conditions using conventional emitters. Owing to the improved spectral resolution obtained using narrow-bore emitters and an analytically derived equation, K$_{d}$ values were simultaneously obtained for at least six ligands to a single druggable protein target from one spectrum for the first time. This research suggests that ligand-protein binding constants can be directly and accurately measured from solutions with high concentrations of nonvolatile buffers and salts by native MS.
    • الموضوع:
      Clinic for Surgery; 610 Medicine & health; Journal Article; PeerReviewed; info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion
    • Note:
      application/pdf
      info:doi/10.5167/uzh-183850
      English
    • Other Numbers:
      CHUZH oai:www.zora.uzh.ch:183850
      https://www.zora.uzh.ch/id/eprint/183850/1/oc8b00787.pdf
      info:doi/10.5167/uzh-183850
      info:doi/10.1021/acscentsci.8b00787
      info:pmid/30834319
      urn:issn:2374-7943
      1416178998
    • Contributing Source:
      HAUPTBIBLIOTHEK UNIV OF ZURICH
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1416178998
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