Monday, February 5
12:30 PM – 1:45 PM
Detecting small molecule non-covalent binders utilizing SAMDI and the Bruker MALDI-TOF – Proof of concept for a new screening format
Presenter: Erica C. VanderPorten
Genentech, South San Francisco, CA
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.
SAMDI Technology: An Innovative Approach to High Throughput Mass Spectrometry
Presenter: Milan Mrksich, PhD
Henry Wade Rodgers Professor in Biomedical Engineering, Chemistry, and Cell and Molecular Biology, Northwestern University, Evanston, IL, Founder of SAMDI Tech Inc.
High-throughput screening is an important tool in drug discovery to identify small molecule modulators of biochemical activities. Most assays rely on cumbersome labels, such as fluorophores, antibodies, and radioisotopes that increase costs and can produce high rates of false-positive hits. Label-free formats address many of these limitations, but current approaches often lack the throughput necessary to accommodate large screening campaigns. Here, we present a label-free, high-throughput assay and apply it to analyze therapeutic targets across a broad range of diseases. The assay combines Self-Assembled-Monolayers on high-density biochip arrays and matrix assisted laser desorption ionization (MALDI) mass spectrometry, a technique termed SAMDI, that enables rapid and quantitative assays capable of screening millions of compounds per day. The ability to directly visualize and measure the reaction intermediates and products not only eliminates false positive hits, but also provides a data-rich output that accelerates drug discovery efforts. Taken together, the SAMDI assay opens avenues for better, faster, label-free, high-throughput screens for a broad range of biochemical activities.
Henry Wade Rodgers Professor in Biomedical Engineering, Chemistry, and Cell and Molecular Biology
Northwestern University, Founder of SAMDI Tech Inc.
Milan is the Henry Wade Rogers Professor at Northwestern University with appointments in the Departments of Chemistry, Biomedical Engineering, and Cell Biology and he is the inventor of the SAMDI technology. His research combines synthetic chemistry with materials science to study important problems in cell biology. He develops biochips for a host of biological and biotechnological applications and develops mimics of the extracellular matrix for studies of cell adhesion and migration. He has patented several chip-based chemical technologies for rapidly screening biological molecules for active compounds. Five years ago, he founded, with Carmichael, Arsenal Medical Inc., a medical devices company that has a stent product in clinical trials. Technology Review magazine named him as a "100 Top Young Innovators" in 2002. He has 150 peer-reviewed publications, including 25 that are based on the SAMDI technology. Milan received his PhD from California Institute of Technology and served a postdoctoral fellowship at Harvard University.
Senior Scientific Researcher
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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