Drug discovery from natural products using affinity selection-mass spectrometry.

Area of Science:

• Biochemistry
• Analytical Chemistry
• Pharmacology

Background:

• Affinity selection-mass spectrometry (AS-MS) is a powerful technique for drug discovery.
• It enables the isolation of pharmacologically active small molecules from complex natural product mixtures.
• AS-MS offers advantages over traditional screening methods, including compatibility with diverse biological components.

Purpose of the Study:

• To highlight the utility of AS-MS as a starting point for drug discovery.
• To describe the principles and successful variations of AS-MS.
• To detail the process of identifying and characterizing lead compounds using AS-MS.

Main Methods:

• Utilizing binding interactions between macromolecular receptors and low molecular mass ligands.
• Employing separation techniques such as pulsed ultrafiltration (PUF) AS-MS, size exclusion chromatography (SEC) AS-MS, and magnetic microbead affinity selection screening (MagMASS).
• Characterizing isolated ligands using high-resolution UHPLC-MS and tandem mass spectrometry, with structural elucidation via 2D NMR and MS.

Main Results:

• AS-MS successfully isolates pharmacologically active small molecules from diverse botanical, fungal, and microbial extracts.
• The method is compatible with various receptors, enzymes, buffers, cofactors, and ligands, requiring no radiolabels or chromophores.
• Identified lead compounds are characterized by elemental composition and structural data, enabling database searching and comparison with standards.

Conclusions:

• AS-MS is an efficient and versatile platform for discovering lead compounds from natural products.
• The technique facilitates rapid characterization and identification of active molecules.
• AS-MS provides a label-free, broadly applicable approach for early-stage drug discovery.