Detecting small molecule non-covalent binders utilizing SAMDI and the Bruker MALDI-TOF – Proof of concept for a new screening format

Recorded On: 10/17/2017

Advances in technology afford the opportunity to revisit old challenges of detecting compound binding from mixtures. We combined the ability of mass spectrometry to unambiguously identify and resolve compounds from complex mixtures of analytes with Self-Assembled Monolayers and matrix-assisted laser Desorption Ionization (SAMDI) technology.   SAMDI technology minimizes “hot spots” by uniformly saturating the surface with captured protein. The ability to wash SAMDI targets decreases interferences from salts and detergents and the Bruker ultrafleXtreme™ MALDI-TOF delivers high resolution data with minimal matrix signal interference.  

This novel screening format uses affinity capture of a target protein of interest that has been incubated with a pool of compounds. Subsequent ionization of the protein and any bound analyte enables the inferred identification of non-covalent compound interactions.  By utilizing a pooled library format and the high speed of the Bruker ultrafleXtreme™ laser, we aim to maximize the throughput of MS-based screening irrespective of enzyme activity. Customized Genedata Expressionist® data analysis workflows identify the hits as masses in each well and hit calling will be determined based on the ratios in samples with protein vs samples without protein.

Erica C. VanderPorten

Senior Scientific Researcher, Genentech

Erica is a Senior Scientific Researcher at Genentech and joined the Department of Biochemical and Cellular Pharmacology in Small Molecule Drug Discovery in 2009. The department develops assays to support medicinal chemistry efforts, characterize and understand compound mechanism of action, and investigate new lead finding technologies. Her recent focus includes exploring mass spectrometry based technologies amenable for high throughput screening. Prior to joining Genentech Erica worked at Sunesis Pharmaceuticals in drug discovery and Five Prime Therapeutics. She obtained her B.S. in Biochemistry and Molecular Biology from the University of California, Davis.

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