2. Academic Validation
  3. Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

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

  • Oncotarget. 2016 Oct 4;7(40):64967-64976. doi: 10.18632/oncotarget.11274.
Qiao Li 1,  Lina Quan 1,  Jiankun Lyu 1,  Zenghui He 1,  Xia Wang 1,  Jiajia Meng 1,  Zhenjiang Zhao 1,  Lili Zhu 1,  Xiaofeng Liu 1,  Honglin Li 1
Affiliations

Affiliation

  • 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.
PMID: 27533458 DOI: 10.18632/oncotarget.11274
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).

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