Trioxane-based MS-cleavable Cross-linking Mass Spectrometry for Profiling Multimeric Interactions of Cellular Networks

Here, we present a novel trioxane-based MS-cleavable homotrifunctional cross-linker TSTO, which can target three proximal lysine residues simultaneously. Owing to its unique structure and MS-cleavability, TSTO enables fast and unambiguous identification of cross-linked peptides using LC-MSn analysis. Importantly, we have demonstrated that the TSTO-based XL-MS platform is effective for mapping PPIs of protein complexes and cellular networks.