Structure-Guided Design of Cyclic Peptide: A Potent Inhibitor Targeting PD-1/PD-L1 Axis with Antitumor Activity.

ABSTRACT: Blocking the protein-protein interaction (PPI) between programmed cell death protein 1 (PD-1) and its ligand PD-L1 is a crucial strategy in cancer immunotherapy. However, existing monoclonal antibody-based therapies have limitations such as high production costs and poor tumor penetration. In this study, we developed a novel cyclic peptide inhibitor, PD-1-0520, through structure-based design. Starting from key fragments of PD-L1 that interact with PD-1, we designed 5 mimetic peptides and further optimized them into 22 cyclic peptide candidates. Through molecular dynamics screening and in vitro and in vivo experimental validation, PD-1-0520 was proven to have potent antitumor activities. Results showed that PD-1-0520 effectively inhibited the PD-1/PD-L1 interaction, restored the immune acti

SUBMITTER: Peng W 

PROVIDER: S-EPMC12692123 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature