文献类型：期刊文献

英文题名：Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

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

年份：2016

卷号：7

期号：40

起止页码：64967

外文期刊名：ONCOTARGET

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000387281000034)】；

基金：The research is supported in part by the National Natural Science Foundation of China (Grants 81302697 and 81230076) (L.Z. and H.L.), and the National Key Research and Development Program (Grant 2016YFA0502304) (H.L.).

语种：英文

外文关键词：immunotherapy; human programmed death 1; peptide inhibitor; protein-protein interactions (PPIs); de novo peptide design

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.