Gay i Marín, MarinaDíaz Lobo, MireiaGusi Vives, MarArauz-Garofalo, GianlucaVilanova, MarGiralt Lledó, ErnestVilaseca Casas, MartaGuardiola Bagán, Salvador2022-04-192023-04-012022-04-011439-7633https://hdl.handle.net/2445/184996We 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.7 p.application/pdfeng(c) Wiley, 2022ProteòmicaTermodinàmicaProteomicsThermodynamicsinfo:eu-repo/semantics/article2022-04-19info:eu-repo/semantics/openAccess654511135362647