Disulfide-Linked Peptides for Blocking BTLA/HVEM Binding
| Autor: | Martyna Maszota-Zieleniak, Valérie Cesson, Vincent Zoete, Katarzyna Kuncewicz, Justyna Iwaszkiewicz, Adam K. Sieradzan, Agnieszka S. Karczyńska, Sylwia Rodziewicz-Motowidło, Laurent Derré, Igor Zhukov, Olivier Michielin, Katarzyna Wegrzyn, Marta Spodzieja, Daniel E. Speiser |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation medicine.medical_treatment animal diseases immune checkpoint inhibitor Crystallography X-Ray lcsh:Chemistry 0302 clinical medicine Disulfides Receptors Immunologic Receptor Peptide sequence lcsh:QH301-705.5 Spectroscopy Chemistry General Medicine Computer Science Applications Cell biology Molecular Docking Simulation 030220 oncology & carcinogenesis immunotherapy biological phenomena cell phenomena and immunity Receptors Tumor Necrosis Factor Member 14 surface plasmon resonance Protein Binding disulfide-linked peptide BTLA chemical and pharmacologic phenomena Catalysis Article Inorganic Chemistry 03 medical and health sciences Mediator Immune system herpes virus entry mediator Cell surface receptor medicine Humans Physical and Theoretical Chemistry Molecular Biology B-and T-lymphocyte attenuator NMR structure molecular docking Binding Sites Organic Chemistry Immunotherapy biochemical phenomena metabolism and nutrition 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 bacteria Cytokine secretion Peptides |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 2 International Journal of Molecular Sciences, Vol 21, Iss 2, p 636 (2020) International journal of molecular sciences, vol. 21, no. 2 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21020636 |
| Popis: | Immune checkpoints are crucial in the maintenance of antitumor immune responses. The activation or blockade of immune checkpoints is dependent on the interactions between receptors and ligands such interactions can provide inhibitory or stimulatory signals, including the enhancement or suppression of T-cell proliferation, differentiation, and/or cytokine secretion. B-and T-lymphocyte attenuator (BTLA) is a lymphoid-specific cell surface receptor which is present on T-cells and interacts with herpes virus entry mediator (HVEM), which is present on tumor cells. The binding of HVEM to BTLA triggers an inhibitory signal which attenuates the immune response. This feature is interesting for studying the molecular interactions between HVEM and BTLA, as they may be targeted for novel immunotherapies. This work was based on the crystal structure of the BTLA/HVEM complex showing that BTLA binds the N-terminal cysteine-rich domain of HVEM. We investigated the amino acid sequence of HVEM and used molecular modeling methods to develop inhibitors of the BTLA/HVEM interaction. We synthesized novel compounds and determined their ability to interact with the BTLA protein and inhibit the formation of the BTLA/HVEM complex. Our results suggest that the HVEM (14&ndash 39) peptide is a potent inhibitor of the formation of the BTLA/HVEM protein complex. |
| Databáze: | OpenAIRE |
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