Light-activated azobenzene peptide inhibitor of the PD-1/PD-L1 interaction

Inhibiting the PD-1/PD-L1 protein-protein interaction is a key immunotherapy for cancer. Antibodies dominate the clinical space but are costly, with limited applicability and immune side effects. We developed a photo-controlled azobenzene peptide that selectively inhibits the PD-1/PD-L1 interaction...

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Published inChemical communications (Cambridge, England) Vol. 6; no. 63; pp. 8228 - 8231
Main Authors Hayward, Deanne, Goddard, Zoë R, Cominetti, Marco M. D, Searcey, Mark, Beekman, Andrew M
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 01.08.2024
The Royal Society of Chemistry
Subjects
Azo compounds
Azo Compounds - chemistry
Azo Compounds - pharmacology
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - metabolism
Chemistry
Humans
Light
Peptides - chemistry
Peptides - pharmacology
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Programmed Cell Death 1 Receptor - metabolism
Protein Binding
Proteins
Side effects
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Summary:Inhibiting the PD-1/PD-L1 protein-protein interaction is a key immunotherapy for cancer. Antibodies dominate the clinical space but are costly, with limited applicability and immune side effects. We developed a photo-controlled azobenzene peptide that selectively inhibits the PD-1/PD-L1 interaction when in the cis isomer only. Activity is demonstrated in in vitro and cellular assays. A photoswitch peptide that binds to PD-1/PD-L1 only in the cis conformation, allowing for external control of the immune checkpoint interaction.
Bibliography:Electronic supplementary information (ESI) available: Synthetic and analytical data for all peptides. See DOI
https://doi.org/10.1039/d4cc01249f
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SourceType-Scholarly Journals-1
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ISSN:1359-7345
1364-548X
1364-548X
DOI:10.1039/d4cc01249f