Disulfide-Linked Peptides for Blocking BTLA/HVEM Binding.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_A28A31EE871C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Disulfide-Linked Peptides for Blocking BTLA/HVEM Binding.
Journal
International journal of molecular sciences
Author(s)
Spodzieja M., Kuncewicz K., Sieradzan A., Karczyńska A., Iwaszkiewicz J., Cesson V., Węgrzyn K., Zhukov I., Maszota-Zieleniak M., Michielin O., Speiser D.E., Zoete V., Derré L., Rodziewicz-Motowidło S.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
18/01/2020
Peer-reviewed
Oui
Volume
21
Number
2
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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 (14-39) peptide is a potent inhibitor of the formation of the BTLA/HVEM protein complex.
Keywords
B-and T-lymphocyte attenuator, NMR structure, disulfide-linked peptide, herpes virus entry mediator, immune checkpoint inhibitor, immunotherapy, molecular docking, surface plasmon resonance
Pubmed
Open Access
Yes
Create date
23/01/2020 15:50
Last modification date
30/04/2021 7:13
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