Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value...

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Detalles Bibliográficos
Autores principales: Li, Qiao, Quan, Lina, Lyu, Jiankun, He, Zenghui, Wang, Xia, Meng, Jiajia, Zhao, Zhenjiang, Zhu, Lili, Liu, Xiaofeng, Li, Honglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323130/
https://www.ncbi.nlm.nih.gov/pubmed/27533458
http://dx.doi.org/10.18632/oncotarget.11274
Descripción
Sumario:Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value of 1.38 ± 0.39 μM, comparable to the binding affinity of the cognate hPD-L1. A Surface Plasmon Resonance (SPR) competitive binding assay result indicated that Ar5Y_4 could inhibit the interaction of hPD-1/hPD-L1. Moreover, Ar5Y_4 could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Peptides described in this paper provide promising biologic candidates for cancer immunotherapy or diagnostics.

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