8p1o

Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives

spinqualitylabelsall models 8p1o, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8p1o is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.17Å Ligands: CL, SO4, WEW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although heavily studied, the subject of anti-PD-L1 small-molecule inhibitors is still elusive. Here we present a systematic overview of the principles behind successful anti-PD-L1 small-molecule inhibitor design on the example of the m-terphenyl scaffold, with a particular focus on the neglected influence of the solubilizer tag on the overall affinity toward PD-L1. The inhibitor developed according to the proposed guidelines was characterized through its potency in blocking PD-1/PD-L1 complex formation in homogeneous time-resolved fluorescence and cell-based assays. The affinity is also explained based on the crystal structure of the inhibitor itself and its costructure with PD-L1 as well as a molecular modeling study. Our results structuralize the knowledge related to the strong pharmacophore feature of the m-terphenyl scaffold preferential geometry and the more complex role of the solubilizer tag in PD-L1 homodimer stabilization. Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives.,Surmiak E, Zaber J, Plewka J, Wojtanowicz G, Kocik-Krol J, Kruc O, Muszak D, Rodriguez I, Musielak B, Viviano M, Castellano S, Skalniak L, Magiera-Mularz K, Holak TA, Kalinowska-Tluscik J ACS Med Chem Lett. 2023 Dec 14;15(1):36-44. doi: 10.1021/acsmedchemlett.3c00306. , eCollection 2024 Jan 11. PMID:38229762 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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