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Peptide Blocking CTLA-4 and B7-1 Interaction

Russian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, Russia
Kizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin St., 634050 Tomsk, Russia
Center for Innovations in Medicine, Biodesign Institute, Arizona State University, 1001 S. McAllister Ave., Tempe, AZ 85281, USA
Author to whom correspondence should be addressed.
Molecules 2021, 26(2), 253;
Received: 18 December 2020 / Revised: 30 December 2020 / Accepted: 2 January 2021 / Published: 6 January 2021
(This article belongs to the Section Molecular Structure)
Discovery of the B7 family immune checkpoints such as CTLA-4 (CD152), PD-1 (CD279), as well as their ligands B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), and B7-DC (PD-L2, CD273), has opened new possibilities for cancer immunotherapy using monoclonal antibodies (mAb). The blockade of inhibitory receptors (CTLA-4 and PD-1) with specific mAb results in the activation of cancer patients’ T lymphocytes and tumor rejection. However, the use of mAb in clinics has several limitations including side effects and cost of treatment. The development of new low-molecular compounds that block immune checkpoints’ functional activity can help to overcome some of these limitations. In this paper, we describe a synthetic peptide (p344) containing 14 amino acids that specifically interact with CTLA-4 protein. A 3D computer model suggests that this peptide binds to the 99MYPPPY104 loop of CTLA-4 protein and potentially blocks the contact of CTLA-4 receptor with B7-1 ligand. Experimental data confirm the peptide-specific interaction with CTLA-4 and its ability to partially block CTLA-4/B7-1 binding. The identified synthetic peptide can be used for the development of novel immune checkpoint inhibitors that can block CTLA-4 functional activity for cancer immunotherapy. View Full-Text
Keywords: peptides; immune checkpoints; peptide microarray; cancer; immunotherapy peptides; immune checkpoints; peptide microarray; cancer; immunotherapy
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MDPI and ACS Style

Podlesnykh, S.V.; Abramova, K.E.; Gordeeva, A.; Khlebnikov, A.I.; Chapoval, A.I. Peptide Blocking CTLA-4 and B7-1 Interaction. Molecules 2021, 26, 253.

AMA Style

Podlesnykh SV, Abramova KE, Gordeeva A, Khlebnikov AI, Chapoval AI. Peptide Blocking CTLA-4 and B7-1 Interaction. Molecules. 2021; 26(2):253.

Chicago/Turabian Style

Podlesnykh, Stepan V., Kristina E. Abramova, Anastasia Gordeeva, Andrei I. Khlebnikov, and Andrei I. Chapoval 2021. "Peptide Blocking CTLA-4 and B7-1 Interaction" Molecules 26, no. 2: 253.

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