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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 μ M 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.
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Metadata
- Authors
- Chang, H., Liu, B., Qi, Y., Zhou, Y., Chen, Y., Pan, K., Li, W., Zhou, X., Ma, W., Fu, C., Qi, Y., Liu, L., & Gao, Y.
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2015-08-10
- Volume
- 54
- Issue
- 40
- Pages
- 11760-11764
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2165838507
- Cited by
- 397
- References
- 12
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Funders
- NSFC (81172893, 91442121, 91313301, 21225207)
- “863” Program of the Ministry of Science and Technology (2012AA02A700)
- National Basic Research Program of China (2013CB932800)
- Outstanding Talent Project of Henan Province (134100510015)
- Zhengzhou University (1421311081)
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- The paper
- Chang, H., Liu, B., Qi, Y., Zhou, Y., Chen, Y., Pan, K., Li, W., Zhou, X., Ma, W., Fu, C., Qi, Y., Liu, L., & Gao, Y. (2015). Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.201506225
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