Protein-protein interactions (PPIs) are the basis of cellular pathways, performing essential regulatory roles. The malfunctions of cell signaling pathways and PPIs have implications in various human disorders, including neurodegenerative diseases and cancers. Mapping of protein interactions in living systems is helpful for the identification of protein complexes that may be potential targets for drug treatment. Unfortunately, it is difficult to identify physiologically relevant PPIs for drug targets, as these interactions are often transient in nature. Chemical cross-linkers coupled with mass spectrometry analysis can be used to map protein-protein interactions and localize their interaction interfaces in living systems. Advantages of chemical cross-linkers include small sample size, tolerance for sample heterogeneity, and automated analysis. Furthermore, collision-induced dissociation (CID) cleavable protein cross-linkers simplify data analysis during cross-linking experiments. Most commercially available cross-linkers target a small subset of the 20 natural amino acids and are not designed to cleave in the mass spectrometer. We have designed and synthesized CID-cleavable protein cross-linkers that target a range of amino acid side chains in order to expand the available cross-linker toolbox.

Efforts toward the synthesis of new collision-induced dissociation cleavable protein cross-linkers

251st National Meeting (2016)

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