Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy.

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.

Total chemical synthesis of the site-selective azide-labeled [I66A]HIV-1 protease.

The first total chemical synthesis of the site-selective azide-labeled [I66A]HIV-1 protease is described by native chemical ligation. Chemical synthesis of azide-labeled proteins would provide useful protein tools for biochemical, biophysical or medical studies.