Structural basis for optimization of molecular probe using P-glycoprotein in vivo imaging

为了开发用于P-糖蛋白体内成像的特异性分子探针，对与探针的一些候选分子复合的P-糖蛋白同系物进行了X射线晶体学分析，并阐明了它们相互作用的结构基础。 从X射线衍射分析中，观察到P-糖蛋白同系物的清晰电子密度，而检测到探针分子的不清晰密度。 络合物晶体的光度测定表明，探针包含在晶体中。 这些结果表明，探针候选人是弱结合在内腔的P-糖蛋白同系物和它们的构象是不固定的，即使在结晶状态。

In order to develop specific molecular probes for in vivo imaging of P-glycoprotein, an X-ray crystallographic analysis of a P-glycoprotein homolog in complex with some candidate molecules for the probe was performed and the structural basis of their interactions was elucidated. From the X-ray diffraction analysis clear electron density of the P-glycoprotein homolog was observed whereas the unclear density of the probe molecules was detected. A photometric assay of the complex crystals indicated that the probes were included in the crystals. These findings indicated that the probe candidates are weakly bound in the inner cavity of the P-glycoprotein homolog and their conformations are unfixed even in the crystalline state.