Paired-probe chemoproteomic strategy enables global site-resolved quantification of lysine redox states

PRISM-Lys enables global, site-resolved quantification of lysine redox stoichiometry by pairing allysine and Lys labeling chemistries, including bidirectional, site-selective remodeling during ferroptosis.

• Why it matters: Lys redox states are poorly mapped because existing methods detect only limited modification sites and rarely measure stoichiometry.
• What they did: The PRISM-Lys platform uses an Am-alkyne probe to enrich allysine via reductive amination and an Ald-alkyne probe to label Lys, with paired reactions producing the same chemical product for isotopic stoichiometry mapping.
• The result: In cells and tissues undergoing ferroptosis, PRISM-Lys shows bidirectional, site-selective changes in Lys oxidation linked to ferroptotic progression, enabling quantitative analysis of protein oxidation.

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