Proteomics

Dataset Information

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A solid-phase compatible silane-based cleavable linker enables custom isobaric quantitative chemoproteomics


ABSTRACT: Only ~4% of the human proteome has been drugged by FDA approved molecules. Consequently, closing this druggability gap is a central focus of mass spectrometry chemoproteomics screening platforms. Despite increasingly widespread adoption, established chemoproteomic platforms fall short of achieving comprehensive proteome-wide structure activity relationship (SAR) maps for two key reasons: (1) time consuming and cumbersome sample preparation workflows and (2) and low throughput sample acquisition. Here we report the silane-based Cleavable Linkers for Isotopically-labeled Proteomics (sCLIP) method. sCLIP streamlines sample preparation with unparalleled early-stage isobaric labeling and sample pooling, allowing for increased sample throughput via customized low cost 6-plex sample multiplexing. The sCLIP method is distinguished by its unprecedented click-assembled isobaric tags, in which the reporter group is encoded in the sCLIP capture reagent and balancer in the pan cysteine-reactive probe. When paired with a custom FragPipe data analysis workflow and applied to cysteine-reactive fragment screens, sCLIP proteomics revealed established and unprecedented cysteine-ligand pairs, including those labeled by covalent-reversible electrophilic modalities.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nik Burton  

LAB HEAD: Keriann Marie Backus

PROVIDER: PXD040696 | Pride | 2023-09-20

REPOSITORIES: Pride

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