In Search of Better Peptide-(Derived from PD-L2)-Based Immune Checkpoint Inhibitors.
Biomolecules
; 14(5)2024 May 18.
Article
in En
| MEDLINE
| ID: mdl-38786004
ABSTRACT
Current anti-cancer immune checkpoint therapy relies on antibodies that primarily target the PD-1/PD-L1(-L2) negative regulatory pathway. Although very successful in some cases for certain cancers, these antibodies do not help most patients who, presumably, should benefit from this type of therapy. Therefore, an unmet clinical need for novel, more effective drugs targeting immune checkpoints remains. We have developed a series of high-potency peptide inhibitors interfering with PD-1/PD-L1(-L2) protein-protein interaction. Our best peptide inhibitors are 12 and 14 amino acids long and show sub-micromolar IC50 inhibitory activity in the in vitro assay. The positioning of the peptides within the PD-1 binding site is explored by extensive modeling. It is further supported by 2D NMR studies of PD-1/peptide complexes. These results reflect substantial progress in the development of immune checkpoint inhibitors using peptidomimetics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Programmed Cell Death 1 Ligand 2 Protein
/
Programmed Cell Death 1 Receptor
/
Immune Checkpoint Inhibitors
Limits:
Humans
Language:
En
Journal:
Biomolecules
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
Switzerland