Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy. Issue 40 (10th August 2015)

• Record Type: Journal Article
• 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
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 40(2015)
• Page Start: 11760
• Page End: 11764
• Publication Date: 2015-08-10
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201506225
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <sc>D</sc>‐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<sc>M</sc> 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 <sc>D</sc>‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.</p> </abstract>