ABSTRACT
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.
Subject(s)
Azo Compounds , B7-H1 Antigen , Light , Peptides , Programmed Cell Death 1 Receptor , Azo Compounds/chemistry , Azo Compounds/pharmacology , Humans , Peptides/chemistry , Peptides/pharmacology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Protein BindingABSTRACT
The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.