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Proteomic tools for the quantitative analysis of artificial peptide libraries: detection and characterization of target-amplified PD-1 inhibitors

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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.

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Articles publicats en revistes (Química Inorgànica i Orgànica)

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Proteomic tools for the quantitative analysis of artificial peptide libraries: detection and characterization of target-amplified PD-1 inhibitors