Disulfide-linked peptides for blocking BTLA/HVEM binding
Marta Spodzieja , Katarzyna Kuncewicz , Adam Sieradzan , Agnieszka Karczyńska , Justyna Iwaszkiewicz , Valérie Cesson , Katarzyna Węgrzyn , Igor Zhukov , Martyna Maszota-Zieleniak , Olivier Michielin , Daniel E. Speiser , Vincent Zoete , Laurent Derre , Sylwia Rodziewicz-Motowidło
AbstractImmune 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, dierentiation, 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 (14–39) peptide is a potent inhibitor of the formation of the BTLA/HVEM protein complex.
|Journal series||International Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)|
|Publication size in sheets||0.85|
|Keywords in English||B-and T-lymphocyte attenuator, herpes virus entry mediator, immunotherapy, immune checkpoint inhibitor, disulfide-linked peptide, NMR structure, molecular docking, surface plasmon resonance|
|ASJC Classification||; ; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 140.0, 22-05-2020, ArticleFromJournal|
|Publication indicators||= 0.000; : 2018 = 1.224; : 2018 = 4.183 (2) - 2018=4.331 (5)|
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