Peptide Blocking CTLA-4 and B7-1 Interaction
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 r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/2/253 |
| _version_ | 1797415932517154816 |
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| author | Stepan V. Podlesnykh Kristina E. Abramova Anastasia Gordeeva Andrei I. Khlebnikov Andrei I. Chapoval |
| author_facet | Stepan V. Podlesnykh Kristina E. Abramova Anastasia Gordeeva Andrei I. Khlebnikov Andrei I. Chapoval |
| author_sort | Stepan V. Podlesnykh |
| collection | DOAJ |
| description | 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 <sup>99</sup>MYPPPY<sup>104</sup> 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. |
| first_indexed | 2024-03-09T05:56:34Z |
| format | Article |
| id | doaj.art-b72bed865dea453997900aeb9a62252e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T05:56:34Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b72bed865dea453997900aeb9a62252e2023-12-03T12:13:07ZengMDPI AGMolecules1420-30492021-01-0126225310.3390/molecules26020253Peptide Blocking CTLA-4 and B7-1 InteractionStepan V. Podlesnykh0Kristina E. Abramova1Anastasia Gordeeva2Andrei I. Khlebnikov3Andrei I. Chapoval4Russian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, RussiaRussian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, RussiaRussian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, RussiaKizhner Research Center, National Research Tomsk Polytechnic University, 30 Lenin St., 634050 Tomsk, RussiaRussian-American Anti-Cancer Center, Altai State University, 61 Lenin St., 656049 Barnaul, RussiaDiscovery 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 <sup>99</sup>MYPPPY<sup>104</sup> 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.https://www.mdpi.com/1420-3049/26/2/253peptidesimmune checkpointspeptide microarraycancerimmunotherapy |
| spellingShingle | Stepan V. Podlesnykh Kristina E. Abramova Anastasia Gordeeva Andrei I. Khlebnikov Andrei I. Chapoval Peptide Blocking CTLA-4 and B7-1 Interaction Molecules peptides immune checkpoints peptide microarray cancer immunotherapy |
| title | Peptide Blocking CTLA-4 and B7-1 Interaction |
| title_full | Peptide Blocking CTLA-4 and B7-1 Interaction |
| title_fullStr | Peptide Blocking CTLA-4 and B7-1 Interaction |
| title_full_unstemmed | Peptide Blocking CTLA-4 and B7-1 Interaction |
| title_short | Peptide Blocking CTLA-4 and B7-1 Interaction |
| title_sort | peptide blocking ctla 4 and b7 1 interaction |
| topic | peptides immune checkpoints peptide microarray cancer immunotherapy |
| url | https://www.mdpi.com/1420-3049/26/2/253 |
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