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Molecules ; 26(2)2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33419027

RESUMEN

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.


Asunto(s)
Antígeno CTLA-4 , Inhibidores de Puntos de Control Inmunológico , Proteínas de Neoplasias , Neoplasias/tratamiento farmacológico , Péptidos , Antígeno B7-1/antagonistas & inhibidores , Antígeno B7-1/química , Antígeno B7-1/metabolismo , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/química , Antígeno CTLA-4/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico/química , Inhibidores de Puntos de Control Inmunológico/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias/química , Neoplasias/metabolismo , Péptidos/química , Péptidos/farmacología
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