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 when in the cis isomer only. Activity is demonstrated in in vitro and cellular assays.

Strategies for converting turn-motif and cyclic peptides to small molecules for targeting protein-protein interactions.

The development of small molecules that interact with protein-protein interactions is an ongoing challenge. Peptides offer a starting point in the drug discovery process for targeting protein-interactions due to their larger, more flexible structure and the structurally diverse properties that allow for a greater interaction with the protein. The techniques for rapidly identifying potent cyclic peptides and turn-motif peptides are highly effective, but this potential has not yet transferred to approved drug candidates. By applying the properties of the peptide-protein interaction the development of small molecules for drug discovery has the potential to be more efficient. In this review, we discuss the methods that allow for the unique binding properties of peptides to proteins, and the methods deployed to transfer these qualities to potent small molecules.