Recent developments in protein–ligand affinity mass spectrometry

This review provides an overview of direct and indirect technologies to screen protein–ligand interactions with mass spectrometry. These technologies have as a key feature the selection or affinity purification of ligands in mixtures prior to detection. Specific fields of interest for these technologies are metabolic profiling of bioactive metabolites, natural extract screening, and the screening of libraries for bioactives, such as parallel synthesis libraries and small combichem libraries. The review addresses the principles of each of the methods discussed, with a focus on developments in recent years, and the applicability of the methods to lead generation and development in drug discovery

Analytics for bioactivity profiling of complex mixtures with a focus on venoms

This chapter introduces bioactivity and bioaffinity terms in relation to mixture profiling and gives the significance of bioactivity and/or bioaffinity profiling of biologically active mixtures in general, and for bioactive mixtures in drug discovery research in particular. Further, the chapter gives an overview of the common and less common analytical approaches for bioactivity profiling of bioactive mixtures. Special focus is put on bioassay-guided fractionation as the standard technique employed (in identification and purification of bioactive molecules from a bioactive mixture), and on state-of-the-art post-column bioactivity profiling approaches, also providing examples and limitations of these analytical methods. On-column and pre-column bioactivity profiling analytics is also discussed. Examples of bioactive molecules identified and purified from different natural products are given with emphasis on molecules isolated from animal venoms. Finally, this chapter briefly discusses the importance of bioactivity profiling of metabolic mixtures in drug discovery