Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy
Journal
Angewandte Chemie - International Edition
Journal Volume
54
Journal Issue
40
Pages
11760-11764
Date Issued
2015
Author(s)
Chang, Hao-Nan
Liu, Bei-Yuan
Qi, Yun-Kun
Zhou, Yang
Chen, Yan-Ping
Pan, Kai-Mai
Li, Wen-Wen
Zhou, Xiu-Man
Ma, Wei-Wei
Fu, Cai-Yun
Qi, Yuan-Ming
Liu, Lei
Gao, Yan-Feng
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.
SDGs
Type
journal article