Dataset Information

A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells

ABSTRACT: Natural systems produce various γ-dicarbonyl-bearing compounds that can covalently modify lysine in protein targets via the classic Paal-Knorr reaction. Among them is a unique class of lipid-derived electrophiles - isoketals that exhibit high chemical reactivity and critical biological functions. However, it remains unknown about their target selectivity and profiles in complex proteomes. Here we report a Paal-Knorr agent, 4-oxonon-8-ynal (herein termed ONAyne), for a proteome-wide selectivity survey and quantitative reactivity profiling of the γ-dicarbonyl warhead. Furthermore, combined with quantitative chemoproteomics in a competitive format, ONAyne permitted global, in situ, and site-specific profiling of targeted lysine residues of two specific isomers of isoketals, levuglandin (LG) D2 and E2. The functional analyses reveal that LGs-derived adduction drives inhibition of malate dehydrogenase MDH2 and exhibits a crosstalk with two epigenetic marks on histone H2B in macrophages. Our approach should be broadly useful for target profiling of bioactive γ-dicarbonyls in diverse biological contexts.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Wang Min-ran

LAB HEAD: Jing Yang

PROVIDER: PXD028270 | Pride | 2022-02-15

REPOSITORIES: Pride

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			Action	DRS
	HFX_HJY_ONA1_R1_20200609_Gradient-Ver1	Other
	HFX_HJY_ONA1_R1_20200609_Gradient-Ver1.raw	Raw
	HFX_HJY_ONA2_R1_20200609_Gradient-Ver1	Other
	HFX_HJY_ONA2_R1_20200609_Gradient-Ver1.raw	Raw
	HFX_HJY_ONAPG-1_R1_20200609_Gradient-Ver1	Other

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A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells.

Wang Min-Ran MR He Jing-Yang JY He Ji-Xiang JX Liu Ke-Ke KK Yang Jing J

Chemical science 20211015 43

Natural systems produce various γ-dicarbonyl-bearing compounds that can covalently modify lysine in protein targets <i>via</i> the classic Paal-Knorr reaction. Among them is a unique class of lipid-derived electrophiles - isoketals that exhibit high chemical reactivity and critical biological functions. However, their target selectivity and profiles in complex proteomes remain unknown. Here we report a Paal-Knorr agent, 4-oxonon-8-ynal (herein termed ONAyne), for surveying the reactivity and sel ...[more]

PMID: 34881007

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