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

被引：48

作者：

Li, Qiao ^{[1
]}

Quan, Lina ^{[1
]}

Lyu, Jiankun ^{[1
]}

He, Zenghui ^{[1
]}

Wang, Xia ^{[1
]}

Meng, Jiajia ^{[1
]}

Zhao, Zhenjiang ^{[1
]}

Zhu, Lili ^{[1
]}

Liu, Xiaofeng ^{[1
]}

Li, Honglin ^{[1
]}

机构：

[1] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 40期

基金：

中国国家自然科学基金;

关键词：

immunotherapy; human programmed death 1; peptide inhibitor; protein-protein interactions (PPIs); de novo peptide design; CANCER-IMMUNOTHERAPY; HOT-SPOTS; WEB SERVER; BINDING; LIGANDS; ENERGY; DETERMINANTS; SIMULATION; EXPRESSION; PREDICTION;

D O I：

10.18632/oncotarget.11274

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 mu M, 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.

引用

页码：64967 / 64976

页数：10

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