Mass spectrometry-cleavable photo-crosslinkers for proteome-wide photo-crosslinking mass spectrometry
By using a compound with diazirine and NHS-carbamate functional groups to create covalent crosslinks in complex samples, the challenges of XL-MS are addressed, enabling efficient detection of protein-protein interactions with high resolution and accuracy.
Patent Information
- Application Number
- PCT/US2024/047461
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-19
- Filing Date
- 2024-09-19
- Publication Date
- 2025-03-27
AI Technical Summary
Current crosslinking mass spectrometry (XL-MS) techniques face challenges in complex samples such as lysates, cells, and tissues due to the N2 problem, where the search space for potential crosslinked peptides scales quadratically with the number of linear peptides, complicating spectral identification and increasing the risk of false discovery.
The development of a compound with a diazirine functional group and an NHS-carbamate functional group, which reacts with proteins to form a conjugate with a urea-based linker. Upon UV irradiation, the diazirine forms a carbene that reacts with nearby proteins, creating covalent crosslinks that are detectable by mass spectrometry.
This approach enables the confident detection of protein-protein interactions in complex samples with residue-level resolution, reducing false discovery rates and providing a method for proteome-wide photo-crosslinking.