Fig. 5: Discovered d-macrocycles bind to a common hydrophobic groove on MDM2.
From: Mirror-image ligand discovery enabled by single-shot fast-flow synthesis of D-proteins
A X-ray co-crystal structures of macrocyclic d-peptides from each cluster to l-MDM2 are shown. Side-chains projecting into the MDM2 surface are highlighted. B The co-crystal structure of d-H101 with MDM2 is shown overlaid with the known d-peptide binder dPMI-δ[1–5, 9–12]18,63 (PDB ID: 6KZU). Side-chains that project into the MDM2 surface are highlighted in the inset. The lowercase d inserted before a single letter amino acid abbreviation denotes d-amino acids. Nle = norleucine. C The co-crystal structure of d-H101 with MDM2 is shown overlaid with the known l-peptide binder and ATSP-704163 (PDB ID: 4N5T). Side-chains that project into the MDM2 surface are highlighted in the inset.
