Rational design of a potent macrocyclic peptide inhibitor targeting the PD-1/PD-L1 protein-protein interaction

被引：10

作者：

Miao, Qi ^{[1
]}

Zhang, Wanheng ^{[1
]}

Zhang, Kuojun ^{[1
]}

Li, He ^{[2
]}

Zhu, Jidong ^{[2
]}

Jiang, Sheng ^{[1
]}

机构：

[1] China Pharmaceut Univ, State Key Lab Nat Med, Sch Pharm, Sch Engn, Nanjing 210009, Peoples R China

[2] Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai, Peoples R China

来源：

RSC ADVANCES | 2021年 / 11卷 / 38期

基金：

中国国家自然科学基金;

关键词：

PREDICTION;

D O I：

10.1039/d1ra03118j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report optimization by rational design of JMPDP-027, a potent cyclic peptide that interferes with the PD-1/PD-L1 protein-protein interaction. JMPDP-027 shows a potent restoring ability towards T-cells with an EC50 of 5.9 nM that is comparable to that of the anti-PD-1 monoclonal antibody pembrolizumab. In addition, JMPDP-027 shows not only high resistance to enzymatic hydrolysis in human serum but also no observable toxicity and potent in vivo anticancer activity comparable to that of the mouse PD-L1 antibody in a colon carcinoma (CT26) model. Cyclic peptide antagonists of this sort may provide novel drug candidates for cancer immunotherapy.

引用

页码：23270 / 23279

页数：10

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