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

doi:10.18632/oncotarget.11274

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Research Papers:

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 and Honglin Li _

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Oncotarget. 2016; 7:64967-64976. https://doi.org/10.18632/oncotarget.11274

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Abstract

Qiao Li1,*, Lina Quan1,*, Jiankun Lyu1, Zenghui He1, Xia Wang1, Jiajia Meng1, Zhenjiang Zhao1, Lili Zhu1, Xiaofeng Liu1, Honglin Li1

1State 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

*These Authors contributed equally to this work

Correspondence to:

Lili Zhu, email: [email protected]

Xiaofeng Liu, email: [email protected]

Honglin Li, email: [email protected]

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

Received: June 06, 2016 Accepted: July 29, 2016 Published: August 12, 2016

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.

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Research Papers:

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

Abstract