The bromodomain-containing protein BAZ2A is a validated target in prostate cancer, while the function of its paralog BAZ2B is still undefined. The bromodomains of BAZ2A and BAZ2B have a very similar binding site for their natural ligand, the acetylated lysine side chain. Here, we present an analysis of the binding modes of eight compounds belonging to three distinct chemical classes. For all compounds, the moiety mimicking the natural ligand makes essentially identical interactions in the BAZ2A and BAZ2B bromodomains. In contrast, the rest of the molecule is partially solvent exposed and shows different orientations and interactions in the two bromodomains. Some of these differences could be exploited for designing selective inhibitors within the BAZ2 bromodomain subfamily.
BT - ChemMedChem C1 - 0235 DA - 2018 May 17 DO - 10.1002/cmdc.201800234 IS - 14 J2 - ChemMedChem LA - eng M3 - Research Article N2 -The bromodomain-containing protein BAZ2A is a validated target in prostate cancer, while the function of its paralog BAZ2B is still undefined. The bromodomains of BAZ2A and BAZ2B have a very similar binding site for their natural ligand, the acetylated lysine side chain. Here, we present an analysis of the binding modes of eight compounds belonging to three distinct chemical classes. For all compounds, the moiety mimicking the natural ligand makes essentially identical interactions in the BAZ2A and BAZ2B bromodomains. In contrast, the rest of the molecule is partially solvent exposed and shows different orientations and interactions in the two bromodomains. Some of these differences could be exploited for designing selective inhibitors within the BAZ2 bromodomain subfamily.
PY - 2018 SE - 1479 SP - 1479 EP - 1487 T2 - ChemMedChem TI - Structural analysis of small molecule binding to the BAZ2A and BAZ2B bromodomains VL - 13 SN - 1860-7187 ER -