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Abstract No.: WeOr-05   [KEYNOTE LECTURE]
Speaker: Renato Zenobi
Session: TOF Analyzers
Presentation date: Wed, Aug 30, 2006
Presentation time: 11:20 – 11:50

Complexomics by Cryodetector MALDI Time-of-Flight Mass Spectrometry

Renato Zenobi1, Nazabal Alexis1, Wenzel Ryan1

1 ETH Zurich, Zurich, Switzerland

Correspondence address: Renato Zenobi, ETH Zurich, Dept of Chemistry and Applied Biosciences, HCI E 329, Zurich, CH-8093 Switzerland.

Web site: http://www.zenobi.ethz.ch/

Keywords: Complex, Non-Covalent; Detector, High Mass; Immunoassay; MALDI.

A rapid, specific and sensitive method for the detection of protein-protein interactions is of crucial importance for drug discovery and clinical diagnostics. Mass spectrometry plays a major role in the analysis of proteins, but its application to the routine analysis of protein complexes has been lagging behind. A new strategy for high throughput analysis of protein-protein interactions will be presented. It is based on a novel cryodetector technology for TOF MS, and chemical cross-linking to stabilize complexes for analysis by MALDI. The methodology allows direct mass spectrometric read-out of antigen-antibody complexes in the 150 - 400 kDa mass range. We demonstrate immunochemical application such as epitope mapping, kinetic studies and sandwich assays. The method is further characterized by very high detection sensitivity (fmol quantities of antigen), high specificity (specific detection of antigen directly in serum), high accuracy, and high speed (minutes per assay), surpassing conventional analytical methods by more than two orders of magnitude. The extension of this strategy to general protein complexomics will also be discussed.