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Oncotarget. 2016 Oct 4;7(40):64967-64976. doi: 10.18632/oncotarget.11274.

Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor.

Author information

1
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

Abstract

Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value of 1.38 ± 0.39 μM, comparable to the binding affinity of the cognate hPD-L1. A Surface Plasmon Resonance (SPR) competitive binding assay result indicated that Ar5Y_4 could inhibit the interaction of hPD-1/hPD-L1. Moreover, Ar5Y_4 could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Peptides described in this paper provide promising biologic candidates for cancer immunotherapy or diagnostics.

KEYWORDS:

de novo peptide design; human programmed death 1; immunotherapy; peptide inhibitor; protein-protein interactions (PPIs)

PMID:
27533458
PMCID:
PMC5323130
DOI:
10.18632/oncotarget.11274
[Indexed for MEDLINE]
Free PMC Article

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