title: Studying protein-protein affinity and immobilized ligand-protein affinity interactions using MS-based methods.
abstract: This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein-protein and protein-immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein-protein and protein-immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS.
authors.affiliation: BioMolecular Analysis, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam, Amsterdam, The Netherlands. j.kool@vu.nl
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kool
authors.forename: Niels
authors.initials: N
authors.lastname: Jonker
authors.forename: Hubertus
authors.initials: H
authors.lastname: Irth
authors.forename: Wilfried M A
authors.initials: WM
authors.lastname: Niessen
mesh_terms: D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D013058:Mass Spectrometry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D055767:Immobilized Proteins; D008024:Ligands; D011506:Proteins