The Application of Fluorine‐Containing Reagents in Structural Proteomics

Structural proteomics refers to large-scale mapping of protein structures in order to understand the relationship between protein sequence, structure, and function. Chemical labeling, in combination with mass-spectrometry (MS) analysis, have emerged as powerful tools to enable a broad range of biological applications in structural proteomics. The key to success is a biocompatible reagent that modifies a protein without affecting its high-order structure. Fluorine, well-known to exert profound effects on the physical and chemical properties of reagents, should have an impact on structural proteomics. In this Minireview, we describe several fluorine-containing reagents that can be applied in structural proteomics. We organize their applications around four MS-based techniques: a) affinity labeling, b) activity-based protein profiling (ABPP), c) protein footprinting, and d) protein cross-linking. Our aim is to provide an overview of the research, development, and application of fluorine-containing reagents in protein structural studies.