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Multi-Tiered Chemical Proteomic Maps of Tryptoline Acrylamide-Protein Interactions in Cancer Cells

ABSTRACT: Covalent chemistry is a versatile approach for expanding the ligandability of the human proteome. Activity-based protein profiling (ABPP) can infer the specific residues modified by electrophilic compounds through competition with broadly reactive probes. Nonetheless, the extent to which such residue-directed ABPP platforms are capable of fully mapping the protein targets of electrophilic compounds in human cells remains unclear. Here, we introduce a complementary approach that directly identifies proteins showing stereoselective reactivity with focused libraries of stereochemically-defined, alkynylated electrophilic compounds. Integration of protein- and cysteine-directed ABPP data from compound-treated human cancer cells revealed generally well-correlated target maps and highlighted specific features, such as protein size and the proteotypicity of cysteine-containing peptides, that help to explain gaps in each ABPP platform. The integrated ABPP strategy furnished stereoselective, high-engagement covalent ligands for > 300 structurally and functionally diverse human proteins, including compounds that modulate enzymes by targeting isotype-restricted and non-catalytic cysteines.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lymphocyte Of B Lineage, B-lymphocyte Cell Line, Epithelial Cell, Prostate Cancer Cell Line

SUBMITTER: EVERT NJOMEN

LAB HEAD: Benjamin F

PROVIDER: PXD042541 | Pride | 2024-06-07

REPOSITORIES: Pride

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	20201123_Ramos_WX-2-16-26-36-46_01.raw	Raw
	20201123_Ramos_WX-2-16-26-36-46_02.raw	Raw
	20201123_Ramos_WX-2-16-26-36-46_03.raw	Raw
	20201123_Ramos_WX-2-16-26-36-46_04.raw	Raw
	20201123_Ramos_WX-2-16-26-36-46_05.raw	Raw

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