Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy

被引：417

作者：

Chang, Hao-Nan ^{[1
]}

Liu, Bei-Yuan ^{[2
]}

Qi, Yun-Kun ^{[1
]}

Zhou, Yang ^{[2
]}

Chen, Yan-Ping ^{[2
]}

Pan, Kai-Mai ^{[1
]}

Li, Wen-Wen ^{[2
]}

Zhou, Xiu-Man ^{[2
]}

Ma, Wei-Wei ^{[3
]}

Fu, Cai-Yun ^{[4
]}

Qi, Yuan-Ming ^{[2
]}

Liu, Lei ^{[1
]}

Gao, Yan-Feng ^{[2
]}

机构：

[1] Tsinghua Univ, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Tsinghua Peking Ctr Life Sci, Minist Educ,Dept Chem, Beijing 100084, Peoples R China

[2] Zhengzhou Univ, Sch Life Sci, Zhengzhou 450001, Henan Province, Peoples R China

[3] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Lab Dynam Immunobiol, Inst Immunobiol,Sch Life Med, Beijing 100084, Peoples R China

[4] Zhejiang Sci Tech Univ, Sch Life Sci, Hangzhou 310018, Zhejiang, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2015年 / 54卷 / 40期

关键词：

antibodies; antitumor agents; cancer immunotherapy; protein chemical synthesis; protein-protein interactions; CHEMICAL-SYNTHESIS; ANTI-PD-L1; ANTIBODY; IMMUNE-SYSTEM; INHIBITORS; DESULFURIZATION; VISUALIZATION; POLYPEPTIDES; DISCOVERY; LIGATION; BLOCKADE;

D O I：

10.1002/anie.201506225

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Blockade of the protein-protein interaction between the transmembrane protein programmed cell death protein 1 (PD-1) and its ligand PD-L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror-image phage display, we developed the first hydrolysis-resistant D-peptide antagonists to target the PD-1/PD-L1 pathway. The optimized compound (D)PPA-1 could bind PD-L1 at an affinity of 0.51 mu m in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated that (D)PPA-1 could also effectively disrupt the PD-1/PD-L1 interaction in vivo. Thus D-peptide antagonists may provide novel low-molecular-weight drug candidates for cancer immunotherapy.

引用

页码：11760 / 11764

页数：5

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