Affinity selection-mass spectrometry screening techniques for small molecule drug discovery

Area of Science:

• Biochemistry
• Analytical Chemistry
• Pharmacology

Background:

• Traditional drug discovery methods face limitations with certain receptor types.
• High-throughput screening (HTS) laboratories are seeking advanced techniques.
• Mass spectrometry (MS) offers sensitive detection capabilities.

Purpose of the Study:

• To highlight the utility of affinity selection-mass spectrometry (AS-MS) in drug discovery.
• To showcase AS-MS as a valuable complement to existing drug discovery technologies.
• To discuss the application of MS in measuring receptor function for drug discovery.

Main Methods:

• AS-MS techniques assess candidate molecule binding to receptors.
• Coupling liquid chromatography-MS with size-based separation methods (e.g., ultrafiltration, gel permeation, size-exclusion chromatography).
• Utilizing MS measurements to evaluate receptor function.

Main Results:

• AS-MS is gaining acceptance in HTS laboratories.
• AS-MS successfully screens a diverse range of receptor types, including difficult targets.
• LC-MS coupled with size-based separations demonstrates significant success across various drug targets.

Conclusions:

• AS-MS techniques are effective complements to traditional drug discovery.
• MS-based screening methods, particularly LC-MS with size-based separations, are highly adaptable and successful.
• MS measurements of receptor function are increasingly valuable for drug discovery.