title: Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Lyu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Zenghui
authors.initials: Z
authors.lastname: He
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D019295:Computational Biology; D045325:HCT116 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C105992:PDCD1 protein, human; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor
keywords: de novo peptide design; human programmed death 1; immunotherapy; peptide inhibitor; protein-protein interactions (PPIs)