Abstract

Affinity selection mass spectrometry (ASMS) is a powerful and generic method for the discovery of compounds that bind to a target protein. The method is based on isolation of target-bound compounds followed by identification of the compounds by mass spectrometry. Most ASMS protocols currently utilize liquid chromatography coupled with mass spectrometry (LC-MS) to analyse the compounds of interest resulting in relatively lengthy analysis times which puts a practical limit on the number of compound that can be screened in a realistic time frame. We have explored the application of acoustic mist ionization mass spectrometry (AMI-MS) for rapid analysis of affinity selection screening. AMI-MS technology uses acoustic droplet injection as a means of directly introducing liquid into the mass spectrometer at sample loading rates of 3 per second, greatly reducing analysis times. We will discuss the AMI-MS methodology as applied to ASMS and present data for several targets that we have screened.