Expansion of Collision Induced Dissociation-Cleavable Protein Cross-linkers for Simplified Tandem Mass Spectrometric Analysis

The three-dimensional structure of a protein determines its physical and chemical properties, and its interactions with other proteins are important for its function. Chemical cross-linking mass spectrometry (XL-MS) has become a powerful and effective approach for the study of protein structure. Unambiguous identification of cross-linked peptides by mass spectrometry has been a challenge, and MS-cleavable cross-linkers provide a practical solution to this problem. We have designed, synthesized, and tested new MS-cleavable cross-linkers built around a cleavable sulfoxide functional group. This project has focused on lysine, tyrosine, and cysteine reactive linkers. These linkers were used to study to protein-protein complexes, elucidating novel structural information