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

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

East China University of Science and Technology

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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 language	English
Pages (from-to)	64967-64976
Number of pages	10
Journal	Oncotarget
Volume	7
Issue number	40
DOIs	https://doi.org/10.18632/oncotarget.11274
State	Published - 2016
Externally published	Yes

Keywords

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

UN SDGs

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

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10.18632/oncotarget.11274

Cite this

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title = "Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor",

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)",

author = "Qiao Li and Lina Quan and Jiankun Lyu and Zenghui He and Xia Wang and Jiajia Meng and Zhenjiang Zhao and Lili Zhu and Xiaofeng Liu and Honglin Li",

year = "2016",

doi = "10.18632/oncotarget.11274",

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T1 - Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

AU - Li, Qiao

AU - Quan, Lina

AU - Lyu, Jiankun

AU - He, Zenghui

AU - Wang, Xia

AU - Meng, Jiajia

AU - Zhao, Zhenjiang

AU - Zhu, Lili

AU - Liu, Xiaofeng

AU - Li, Honglin

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - De novo peptide design

KW - Human programmed death 1

KW - Immunotherapy

KW - Peptide inhibitor

KW - Protein-protein interactions (PPIs)

UR - https://www.scopus.com/pages/publications/84994121038

U2 - 10.18632/oncotarget.11274

DO - 10.18632/oncotarget.11274

M3 - 文章

C2 - 27533458

AN - SCOPUS:84994121038

SN - 1949-2553

VL - 7

SP - 64967

EP - 64976

JO - Oncotarget

JF - Oncotarget

IS - 40

ER -

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

Abstract

Keywords

UN SDGs

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