Proteomics

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


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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Marina Gay  

LAB HEAD: Marta Vilaseca

PROVIDER: PXD028412 | Pride | 2022-04-19

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
3558_SG_VC1_nanoC8_After_R08.raw Raw
3558_SG_VC1_nanoC8_Before_R07.raw Raw
3558_SG_VC2_nanoC8_After_R10.raw Raw
3558_SG_VC2_nanoC8_Before_R09.raw Raw
3558_SG_VC3_nanoC8_After_R12.raw Raw
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Publications

Proteomic Tools for the Quantitative Analysis of Artificial Peptide Libraries: Detection and Characterization of Target-Amplified PD-1 Inhibitors.

Gay Marina M   Díaz-Lobo Mireia M   Gusi-Vives Mar M   Arauz-Garofalo Gianluca G   Vilanova Mar M   Giralt Ernest E   Vilaseca Marta M   Guardiola Salvador S  

Chembiochem : a European journal of chemical biology 20220411 12


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 sa  ...[more]

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