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

  • Qiao Li
  • , Lina Quan
  • , Jiankun Lyu
  • , Zenghui He
  • , Xia Wang
  • , Jiajia Meng
  • , Zhenjiang Zhao
  • , Lili Zhu*
  • , Xiaofeng Liu
  • , Honglin Li
  • *Corresponding author for this work
  • East China University of Science and Technology

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)64967-64976
Number of pages10
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - 2016
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • De novo peptide design
  • Human programmed death 1
  • Immunotherapy
  • Peptide inhibitor
  • Protein-protein interactions (PPIs)

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