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
收藏
页码：64967 / 64976
页数：10
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