Analyzing Biomolecular Interactions By Mass Spectrometry.pdf
This monograph reviews all relevant technologies based on mass spectrometry that are used to study or screen biological interactions in general. Arranged in three parts, the text begins by reviewing techniques nowadays almost considered classical, such as affinity chromatography and ultrafiltration, as well as the latest techniques. The second part focusses on all MS-based methods for the study of interactions of proteins with all classes of biomolecules. Besides pull down-based approaches, this section also emphasizes the use of ion mobility MS, capture-compound approaches, chemical proteomics and interactomics. The third and final part discusses other important technologies frequently employed in interaction studies, such as biosensors and microarrays. For pharmaceutical, analytical, protein, environmental and biochemists, as well as those working in pharmaceutical and analytical laboratories.
Jeroen Kool focussed in his PhD study on the integration of chemical and biochemical detection after separation methodologies. Following his PhD, he was responsible for target evaluation, hit screening and identification, and lead optimization processes at Kiadis Pharma (The Netherlands). He continued his academic career in 2005 as a post-doc in the Biomolecular Mass Spectrometry group in Utrecht working on proteomics and biomarker discovery. From 2007 to present, he is responsible for the research line Bioanalytical Screening Methodologies at the VU University Amsterdam (The Netherlands) with a particular focus on hyphenated analytical techniques combining mass spectrometry and chromatography with novel bioassay techniques for bioactive mixture analysis. He published over 40 peer reviewed articles and one book chapter. Wilfried Niessen studied chemistry at the VU University of Amsterdam. After his PhD, he worked for 9 years as an analytical chemist within the Leiden/Amsterdam Center for Drug Research at Leiden University (The Netherlands). After leaving the university in 1996, he started the company hyphen MassSpec, providing independent consultancy and training in the field of analytical mass spectrometry. In parallel to his consultant activities, he was appointed extraordinary professor in bioanalytical mass spectrometry at the Faculty of Science of the VU University in Amsterdam in 2002. He is currently Interim Head of the Division BioMolecular Analysis and Spectroscopy at VU University Amsterdam. His main research interests involve principles, instrumentation and applications of liquid chromatography-mass spectrometry as well as interpretation of small-molecule MS/MS mass spectra. He is (co)author of more than 180 publications in the field of LC-MS in refereed international journals and more than 30 book chapters. Wilfried Niessen authored and edited five books, and was guest editor on several special journal issues.
PART A: SMALL LIGANDS PART A1. Assays without chromatography 1. MS based binding assays in MTPs, involving separation of bound and non-bound ligands 2. Rapidfire technology and alike technologies 3. Microarray MS-based binding assays with MALDI FlashQuant technology and similar technologies PART A2. Pre-column bioassays 4. Pre-column affinity assessment (SPE) via binding to immobilized targets and direct detection after separation of bound and non-bound with flow-based technology 5. Solution-phase affinity selection involving ultrafiltration and pulsed ultrafiltration 6. Size exclusion chromatography - ALIS system PART A3. On-column bioassays: affinity chromatography 7. Frontal and zonal affinity chromatography coupled to MS PART A4. Post-column on-line and at-line bioassays 8. On-line liquid chromatography (LC)-bioassays (post-column continuous-flow systems) 9. Assaying small molecule-receptor interactions by continuous flow competitive displacement chromatography/mass spectrometry 10. Microfluidics in MS-based bioassays 11. At-line and off-line technologies such as Effect Directed Analysis (also environmental) and micro- and nano-fractionation technologies 12. Metabolic profiling approaches for identification of bioactive metabolites PART B: PROTEIN LIGANDS 13. Studying protein-protein interactions in the gas phase with MS 14. Studying protein-small ligand interactions in the gas phase with MS 15. Studying protein-nucleotide interactions in the gas phase with MS 16. Studying protein-carbohydrate interactions in the gas phase with MS 17. Studying protein-lipid interactions in the gas phase with MS (including membrane protein association with lipids) 18. Native MS approaches using ion-mobility MS 19. Study of cellular protein complexes involved in signaling events with pull-down-based interaction proteomics. Interactomics. Including tandem affinity purification. Affinity capture mass spectrometry for studying protein interactions. 20. Chemical proteomics to screen selectivity profiles of ligands for multiple drug targets and off-targets PART C: MISCELLANEOUS APPROACHES 21. Affinity capillary electrophoresis, using mobility shift and/or immobilized protein methods 22. Surface plasmon resonance-MS for protein and/or small ligand affinity analysis, quantification, and identification 23. Other biosensor and surface technologies coupled to MS 24. Microfluidics and microarray technologies towards affinity analysis with MS