Discovery of d -Miniprotein Inhibitors of PD-1/PD-L1 Interaction via Mirror-Image Phage Display against Synthetic d -PD-1

and PD-1 was studied by NMR and MD simulations. For comparison, we screened several commercial and in-house short peptide libraries against synthetic d-PD-1. The failure in identifying a hit structure with inhibition activity using those libraries underpins the superiority of the well-folded miniprotein library in PPI inhibitor development for challenging protein targets.