Disulfide-Linked Peptides for Blocking BTLA/HVEM Binding.
- Spodzieja M Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- Kuncewicz K Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- Sieradzan A Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- Karczyńska A Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- Iwaszkiewicz J SIB Swiss Institute of Bioinformatics, Quartier Sorge, Bâtiment Amphipole, CH-1015 Lausanne, Switzerland.
- Cesson V Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland.
- Węgrzyn K Intercollegiate Faculty of Biotechnology UG&MUG, University of Gdansk, Abrahama 58, 80-308 Gdańsk, Poland.
- Zhukov I Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warszawa, Poland.
- Maszota-Zieleniak M Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- Michielin O SIB Swiss Institute of Bioinformatics, Quartier Sorge, Bâtiment Amphipole, CH-1015 Lausanne, Switzerland.
- Speiser DE Department of Oncology, University of Lausanne, Ch. des Boveresses 155, CH-1066 Lausanne, Switzerland.
- Zoete V SIB Swiss Institute of Bioinformatics, Quartier Sorge, Bâtiment Amphipole, CH-1015 Lausanne, Switzerland.
- Derré L Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland.
- Rodziewicz-Motowidło S Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
- 2020-01-23
Published in:
- International journal of molecular sciences. - 2020
B-and T-lymphocyte attenuator
NMR structure
disulfide-linked peptide
herpes virus entry mediator
immune checkpoint inhibitor
immunotherapy
molecular docking
surface plasmon resonance
Binding Sites
Crystallography, X-Ray
Disulfides
Humans
Models, Molecular
Molecular Docking Simulation
Peptides
Protein Binding
Protein Conformation
Receptors, Immunologic
Receptors, Tumor Necrosis Factor, Member 14
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.3390/ijms21020636
- PMID 31963646
- Persistent URL
- https://sonar.ch/global/documents/83104
Export to…
Statistics
Document views: 53
File downloads:
- Full-text: 0