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High-Throughput Screening of Amyloid Inhibitors via Covalent-Labeling Mass Spectrometry

ABSTRACT: MS spectra of DEPC modifications on beta-2-microglobulin (b2m) residues under amyloid-forming conditions, with or without 4-hydroxythalidomide.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Richard W. Vachet

PROVIDER: MSV000098322 | MassIVE | Wed Jun 25 09:42:00 BST 2025

REPOSITORIES: MassIVE

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High-Throughput Screening of Amyloid Inhibitors via Covalent-Labeling Mass Spectrometry.

Khamnong Kanitin K Stahl Vanessa L VL Izikson Olivia N ON Devarajan Anirudh A Thayumanavan S S Vachet Richard W RW

Analytical chemistry 20250619 25

Amyloid fibril formation by proteins is implicated in numerous human diseases, yet few treatments exist in part due to the lack of robust screening methods for amyloid inhibitors. Here, we demonstrate a novel mass spectrometry (MS) assay for high-throughput screening of amyloid inhibitors, based on measuring the extent of protein labeling during protein aggregation. Amyloid formation decreases covalent labeling (CL) extents, while the presence of an inhibitor restores the extent of labeling, pro ...[more]

PMID: 40537900

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