Next Article in Journal
ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5
Previous Article in Journal
Proteomic Analysis of the Resistance Mechanisms in Sugarcane during Sporisorium scitamineum Infection
Article

Design and Synthesis of A PD-1 Binding Peptide and Evaluation of Its Anti-Tumor Activity

by 1,2, 1, 1, 1,2, 1,*,† and 1,3,*,†
1
The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, China
2
Department of Medical Microbiology, Faculty of Sciences, Ibb University, Ibb City 70270, Yemen
3
Nanjing Anji Biotechnology Co. Ltd., Nanjing 210046, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(3), 572; https://doi.org/10.3390/ijms20030572
Received: 11 January 2019 / Revised: 26 January 2019 / Accepted: 27 January 2019 / Published: 29 January 2019
(This article belongs to the Section Biochemistry)
Immune-checkpoint blockades, suchas PD-1 monoclonal antibodies, have shown new promising avenues to treat cancers. Failure responsesof many cancer patients to these agents have led to a massive need for alternative strategies to optimize tumor immunotherapy. Currently, new therapeutic developments involve peptide blocking strategies, as they have high stability and low immunogenicity. Here, we have designed and synthesized a new peptide FITC-YT-16 to target PD-1. We have studied FITC-YT-16 by various experiments, including Molecular Operating Environment MOE modeling, purification testing by HPLC and LC mass, peptide/PD-1 conjugation and affinity by microscale thermophoresis (MST), and T cell immune-fluorescence imaging by fluorescence microscopy and flow cytometry. The peptide was tested for its ability to enhanceT cell activity against tumor cell lines, including TE-13, A549, and MDA-MB-231. Lastly, we assessed T cell cytotoxicity under peptide treatment. YT-16–PD-1 interaction showed a high binding affinity as a low energy complex that was confirmed by MOE. Furthermore, the peptide purity and molecular weights were 90.96% and 2344.66, respectively. MST revealed that FITC-YT-16 interacted with PD-1 at a Kd value of 17.8 ± 2.6 nM. T cell imaging and flow cytometry revealed high affinity of FITC-YT-16 to PD-1. Interestingly, FITC-YT-16 efficiently blocked PD-1 signaling pathways and promoted T cell inflammatory responses by elevating IL-2 and INF-γ levels. Moreover, FITC-YT-16 has the ability to activate T cell cytotoxicity. Therefore, FITC-YT-16 significantly enhanced T cell anti-tumor activity by blocking PD-1–PD-L1 interactions. View Full-Text
Keywords: T cells; PD-1; PD-L1; FITC-YT-16 peptide; tumor; cytokines T cells; PD-1; PD-L1; FITC-YT-16 peptide; tumor; cytokines
Show Figures

Graphical abstract

MDPI and ACS Style

Abbas, A.B.; Lin, B.; Liu, C.; Morshed, A.; Hu, J.; Xu, H. Design and Synthesis of A PD-1 Binding Peptide and Evaluation of Its Anti-Tumor Activity. Int. J. Mol. Sci. 2019, 20, 572. https://doi.org/10.3390/ijms20030572

AMA Style

Abbas AB, Lin B, Liu C, Morshed A, Hu J, Xu H. Design and Synthesis of A PD-1 Binding Peptide and Evaluation of Its Anti-Tumor Activity. International Journal of Molecular Sciences. 2019; 20(3):572. https://doi.org/10.3390/ijms20030572

Chicago/Turabian Style

Abbas, Abdul B., Bingjing Lin, Chen Liu, Arwa Morshed, Jialiang Hu, and Hanmei Xu. 2019. "Design and Synthesis of A PD-1 Binding Peptide and Evaluation of Its Anti-Tumor Activity" International Journal of Molecular Sciences 20, no. 3: 572. https://doi.org/10.3390/ijms20030572

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop