(1048-A) Affinity selection-mass spectrometry towards membrane protein drug discovery

Abstract: Hit Identification (Hit-ID) is a key step in drug discovery. High-throughput screening (HTS) based on biochemical assays has been dominating the past 30 years but new paradigms like Fragment Based Drug Discovery (FBDD) [1] or DNA Encoded Library Technology (DELT) [2] have provided complementary approaches to explore challenging targets and extend the boundaries of chemical spaces addressable. More recently methods based on Mass Spectrometry (MS) readouts have emerged as new high-throughput technologies in Hit-ID [3]. Thanks to the great sensitivity achieved with new-generation mass spectrometers, specific target-ligand interactions can be assessed in complex mixtures with no need to label the target nor the ligand. Among these technologies, Affinity Selection-Mass Spectrometry (AS-MS) has proved to be valuable in the exploration of targets that have failed with other methods [4]. The historical development of this approach and the latest breakthroughs will be presented with a particular focus on membrane proteins. We have indeed used AS-MS to screen our proprietary, natural product-like Keymical Space™ and identified allosteric binders of a class A GPCR. Our effort towards screening Ion-channels will be also presented.





References:

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