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Bio-affinity characterization mass spectrometry

J E Bruce1, G A Anderson, R Chen

  • 1Chemical Sciences Department, Pacific Northwest Laboratory, Richland, Washington 99352, USA.

Rapid Communications in Mass Spectrometry : RCM
|January 1, 1995
PubMed
Summary
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Bio-affinity characterization mass spectrometry (BACMS) offers a rapid, sensitive method for analyzing noncovalent interactions in solution. This technique avoids solid supports and enables high-throughput screening for drug development.

Area of Science:

  • Analytical Chemistry
  • Biochemistry
  • Mass Spectrometry

Background:

  • Characterizing noncovalent interactions in complex mixtures is crucial for drug discovery.
  • Existing methods like affinity chromatography have limitations, including solid support requirements and potential artifacts.
  • A need exists for faster, more sensitive, and flexible techniques to analyze these interactions.

Purpose of the Study:

  • To introduce and describe bio-affinity characterization mass spectrometry (BACMS) as a novel approach.
  • To demonstrate BACMS's capability for rapid and sensitive analysis of noncovalent interactions in solution.
  • To highlight its potential applications in high-throughput screening for drug development.

Main Methods:

  • Utilizes Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry coupled with electrospray ionization (ESI).

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  • Leverages FTICR's high-resolution mass analysis and MSn capabilities.
  • Incorporates advanced quadrupolar excitation techniques, such as selected-ion accumulation.

    • Main Results:

    • BACMS enables direct investigation of specific noncovalent complexes formed in solution.
    • Demonstrates extraordinary sensitivity, achieving detection at 1 x 10^-9 M solution concentration without prior separation.
    • Successfully analyzes very low relative concentration noncovalent associations.

    Conclusions:

    • BACMS provides a rapid, sensitive, and flexible alternative for characterizing noncovalent interactions.
    • The method avoids solid-phase limitations and artifacts associated with traditional techniques.
    • BACMS is well-suited for combinatorial mixture screening and analysis in drug discovery.