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Tyrosine/Lysine-Targeting Urazole Cross-Linkers for Protein Structural Analysis

ABSTRACT: Chemical cross-linking mass spectrometry (XL-MS) is essential for studying protein structures and interactions. While lysine-targeted cross-linkers dominate current applications, this study introduces two urazole-derived MS-cleavable cross-linkers for tyrosine and lysine residues. A homobifunctional cross-linker (SBT) targets tyrosine via electrochemical click chemistry, while a heterobifunctional cross-linker (SCT) binds both lysine and tyrosine. Their efficiency was validated through reactions with peptides, proteins, and complexes. Additionally, AlphaFold 3-predicted BSA dimer structures were compared with crystallographic data, revealing improved structural coverage. These cross-linkers expand the XL-MS toolkit, enhancing protein structural analysis accuracy and scope.

ORGANISM(S): Mus Musculus

SUBMITTER: Zhonglin Wei

PROVIDER: PXD060590 | iProX | Fri Feb 07 00:00:00 GMT 2025

REPOSITORIES: iProX

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