Native MS: an 'ESI' way to support structure- and fragment-based drug discovery

Area of Science:

• Biochemistry
• Analytical Chemistry
• Pharmacology

Background:

• Drug discovery requires integrating diverse technologies for optimizing hit/lead compounds.
• Biophysical methods are crucial for assessing compound-target interactions.
• Native mass spectrometry (MS) has emerged as a powerful tool in this domain.

Purpose of the Study:

• To review the application of native MS in compound-binding screening.
• To discuss the characterization of ligand-binding properties using native MS.
• To highlight native MS's role in structure- and fragment-based drug research.

Main Methods:

• Description of the general approach of native MS for screening.
• Overview of characterizing ligand-binding properties via native MS.
• Literature and internal development examples illustrating native MS applications.

Main Results:

• Native MS is a highly sensitive and accurate screening technique.
• The method provides in-depth characterization of ligand-binding properties.
• Native MS supports structure- and fragment-based drug discovery efforts.

Conclusions:

• Native MS demonstrates significant potential for detailed ligand-binding analysis.
• It serves as a reliable screening technique within drug discovery pipelines.
• The integration of native MS enhances the optimization of therapeutic compounds.