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Updated: Sep 28, 2025
Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
Proteomic Tools for the Quantitative Analysis of Artificial Peptide Libraries: Detection and Characterization of
Marina Gay1, Mireia Díaz-Lobo1, Mar Gusi-Vives1
1Institute for Research in Biomedicine (IRB Barcelona), BIST (Barcelona Institute of Science and Technology), Baldiri Reixac 10, Barcelona, 08028, Spain.
Abstract:
We report a quantitative proteomics data analysis pipeline, which coupled to protein-directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein-protein interaction (PPI) modulators. A low-affinity PD-1 binder was incubated with a library of >100 D-peptides under thiol-exchange favoring conditions, in the presence of the target protein PD-1, and we determined the S-linked dimeric species that resulted, amplified in the protein samples versus the controls. We chemically synthesized the target dimer candidates and validated them by thermophoresis binding and protein-protein interaction assays. The results provide a proof-of-concept for using this strategy in the high-throughput search of improved drug-like peptide binders that block therapeutically relevant protein-protein interactions.
