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- Title
Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy.
- Authors
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 DPPA-1 could bind PD-L1 at an affinity of 0.51 μ M in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated that DPPA-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.
- Subjects
PROTEIN-protein interactions; CANCER immunotherapy; MEMBRANE proteins; APOPTOSIS; ANTINEOPLASTIC agents; PEPTIDE synthesis; CIRCULAR dichroism
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 40, p11926
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201506225