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• W4386567064 endingPage "126811" @default.
• W4386567064 startingPage "126811" @default.
• W4386567064 abstract "The current research in tumor immunotherapy indicates that blocking the protein-protein interaction (PPI) between PD-1 and its ligand, PD-L1, may be one of the most effective treatments for cancer patients. The α-helix is a common elements of protein secondary structure and is often involved in protein interaction. Thus, α-helix-based peptides could mimic proteins involved in such interactions and are also capable of modulating PPI in vivo. In this study, starting from a potential α-helix-rich protein, we designed a series of α-helix-based peptide candidates to block PD-1/PD-L1 interaction. These candidates were first screened using molecular docking and molecular dynamics simulations, and then their capacities to inhibit PD-1/PD-L1 interactions and to restore antitumor immune activities were investigated using the HTRF assay, SPR assay, cellular co-culture experiments and animal model experiments. Two peptides exhibited the best anti-tumor effects and the strong ability to restore the immunity of tumor-infiltrating T-cells. Further D-amino acid substitution was employed to improve the serum stability of peptide candidate, making the intravenous administration easier while maintaining the therapeutic efficacy. The resultant peptides showed promise as checkpoint inhibitors for application in tumor immunotherapy. These findings suggested that our strategy for developing peptides starting from an α-helical structure could be used in the design of bioactive inhibitors to potential block protein-protein interactions." @default.
• W4386567064 created "2023-09-10" @default.
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• W4386567064 date "2023-12-01" @default.
• W4386567064 modified "2023-10-17" @default.
• W4386567064 title "Design and evaluation of α-helix-based peptide inhibitors for blocking PD-1/PD-L1 interaction" @default.
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• W4386567064 doi "https://doi.org/10.1016/j.ijbiomac.2023.126811" @default.
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• W4386567064 hasPublicationYear "2023" @default.
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