表面等离子共振
虚拟筛选
对接(动物)
免疫原性
化学
生物信息学
肽
药物发现
计算生物学
生物物理学
抗体
生物化学
纳米技术
医学
生物
材料科学
免疫学
纳米颗粒
基因
护理部
作者
Yuanqiang Wang,Haiqiong Guo,Zhiwei Feng,Siyi Wang,Yuxuan Wang,Qingxiu He,Guangping Li,Weiwei Lin,Xiang-Qun Xie,Zhihua Lin
出处
期刊:Molecules
[MDPI AG]
日期:2019-10-21
卷期号:24 (20): 3784-3784
被引量:19
标识
DOI:10.3390/molecules24203784
摘要
The blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a critical role in cancer immunotherapy by reducing the immune escape. Five monoclonal antibodies that antagonized PD-1/PD-L1 interaction have been approved by the Food and Drug Administration (FDA) and marketed as immunotherapy for cancer treatment. However, some weaknesses of antibodies, such as high cost, low stability, poor amenability for oral administration, and immunogenicity, should not be overlooked. To overcome these disadvantages, small-molecule inhibitors targeting PD-L1 were developed. In the present work, we applied in silico and in vitro approaches to develop short peptides targeting PD-1 as chemical probes for the inhibition of PD-1–PD-L1 interaction. We first predicted the potential binding pocket on PD-1/PD-L1 protein–protein interface (PPI). Sequentially, we carried out virtual screening against our in-house peptide library to identify potential ligands. WANG-003, WANG-004, and WANG-005, three of our in-house peptides, were predicted to bind to PD-1 with promising docking scores. Next, we conducted molecular docking and molecular dynamics (MD) simulation for the further analysis of interactions between our peptides and PD-1. Finally, we evaluated the affinity between peptides and PD-1 by surface plasmon resonance (SPR) binding technology. The present study provides a new perspective for the development of PD-1 inhibitors that disrupt PD-1–PD-L1 interactions. These promising peptides have the potential to be utilized as a novel chemical probe for further studies, as well as providing a foundation for further designs of potent small-molecule inhibitors targeting PD-1.
科研通智能强力驱动
Strongly Powered by AbleSci AI