title: Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy.
abstract: 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 μM 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.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China).
authors.forename: Hao-Nan
authors.initials: HN
authors.lastname: Chang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Bei-Yuan
authors.initials: BY
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China).
authors.forename: Yun-Kun
authors.initials: YK
authors.lastname: Qi
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China).
authors.forename: Kai-Mai
authors.initials: KM
authors.lastname: Pan
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Li
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Xiu-Man
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunobiology, School of Life Medicine, Tsinghua University, Beijing 100084 (China).
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Ma
authors.affiliation: School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province (China).
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Fu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China).
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Qi
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). lliu@mail.tsinghua.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). gaoyf@zzu.edu.cn.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Gao
keywords: antibodies; antitumor agents; cancer immunotherapy; protein chemical synthesis; protein-protein interactions