Abstract

Affinity Selection-Mass Spectrometry (AS-MS) has been used successfully in high-throughput screening since nearly 20 years. This label-free technology has gaining popularity as alternative to traditional biochemical approaches for a rapid assessment on the ligandability of a target. In addition, the technology is economical as large collections can be screened as pool of compounds.
The AS-MS screening process implemented at Edelris can be decomposed in three main steps. The first step consists in the incubation of the target with mixtures of possible ligands from a 2M compound collection derived from our natural product-like Keymical Space™. Then, unbound compounds are removed from ligand-target complexes by a parallelized size-exclusion chromatography. Finally, target-ligand complexes previously isolated are dissociated and characterized in one step by LC/HRMS. This last step is central for accurate ligand identification yet is also the limiting step of the process. In this presentation, analytical improvements implemented to increase the sensibility, repeatability and throughput will be presented.