A photo-caged cross-linker for identifying protein-protein interactions

In recent years cross-linking mass spectrometry (XL-MS) as a tool to study protein-protein interactions (PPIs) has undergone significant improvements, which were mainly propelled by the emergence of novel crosslinkers and the development and implementation of advanced analysis workflows. Despite these recent advancements, addressing PPIs in the cell by XL-MS remains a substantial challenge. Some of the current limitations are linked to a comparable poor membrane permeability of most crosslinkers and their limited efficiency to traverse the cellular membrane. To address this problem, we have designed and synthesized a novel crosslinker based on the chemical o-nitrobenzylester (o-NBE) group, which enhances the hydrophobic properties of the cross-linker.