[Molecular docking study and experimental evaluation of potential CTLA-4 binding peptides]
| Autor: | V V Lampatov, Andrei Chapoval, S. V. Podlesnykh, Andrei I. Khlebnikov |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.drug_class medicine.medical_treatment chemical and pharmacologic phenomena Peptide Computational biology Monoclonal antibody General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system Antineoplastic Agents Immunological Cancer immunotherapy medicine Humans CTLA-4 Antigen chemistry.chemical_classification biology General Medicine Immunotherapy Ligand (biochemistry) Molecular Docking Simulation 030104 developmental biology chemistry CTLA-4 030220 oncology & carcinogenesis biology.protein Antibody Peptides |
| Zdroj: | Biomeditsinskaia khimiia. 66(2) |
| ISSN: | 2310-6972 |
| Popis: | Current advances in research of immune checkpoints CTLA-4, PD-1, PD-L1, opened new possibilities for effective cancer immunotherapy using monoclonal antibodies. However, antibodies have a number of limitations for clinical use, which provides a basis for the search for low molecular weight compounds capable of regulating (blocking) molecules that inhibit the immune response. This paper presents the results of molecular docking and evaluation of synthetic peptide interaction with a CTLA-4 molecule. Using mathematical modeling, it was shown that peptides interacted with the 99MYPPPY104 loop of the CTLA-4 protein and could potentially block the interaction of the CTLA-4 receptor with its natural ligand B7-1. The specificity of the interaction between the identified peptide and recombinant chimeric CTLA-4 protein was evaluated. The detected synthetic peptide can be used for the development of immunomodulatory drugs for therapy of cancer or autoimmune diseases.Sovremennye dostizheniia v izuchenii svoĭstv molekul kontrolia immuniteta (tak nazyvaemykh immunologicheskikh kontrol'nykh tochek – “chekpoĭntov”) CTLA-4, PD-1, PD-L1 otkryli novye vozmozhnosti dlia éffektivnoĭ terapii onkologicheskikh zabolevaniĭ s pomoshch'iu monoklonal'nykh antitel. Odnako preparaty antitel imeiut riad ogranicheniĭ, chto aktualiziruet poisk nizkomolekuliarnykh soedineniĭ, sposobnykh regulirovat' (blokirovat') funktsii molekul, ingibiruiushchikh immunnyĭ otvet. V nastoiashcheĭ rabote predstavleny rezul'taty molekuliarnogo dokinga i éksperimental'nogo izucheniia spetsifichnosti vzaimodeĭstviia sinteticheskikh peptidov s molekuloĭ CTLA-4. S pomoshch'iu matematicheskogo modelirovaniia bylo pokazano, chto odin iz issleduemykh peptidov vzaimodeĭstvuet s petleĭ 99MYPPPY104 belka CTLA-4 i potentsial'no mozhet blokirovat' vzaimodeĭstvie CTLA-4 retseptora s ego prirodnym ligandom B7-1. Provedena éksperimental'naia otsenka spetsifichnosti vzaimodeĭstviia vyiavlennogo peptida s rekombinantnymi khimernymi belkami CTLA-4 i V7-1. Poluchennyĭ sinteticheskiĭ peptid mozhet byt' ispol'zovan dlia razrabotki immunomoduliruiushchikh preparatov dlia terapii onkologicheskikh ili autoimmunnykh zabolevaniĭ. |
| Databáze: | OpenAIRE |
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