Pontillo Nicola, Ferraro Giarita, Helliwell John R, Amoresano Angela, Merlino Antonello
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Napoli, Italy.
School of Chemistry, Faculty of Engineering and Physical Sciences, University of Manchester, Brunswick Street, Manchester M13 9PL, England.
ACS Med Chem Lett. 2017 Feb 28;8(4):433-437. doi: 10.1021/acsmedchemlett.7b00025. eCollection 2017 Apr 13.
The second-generation Pt anticancer agent carboplatin (CBDCA) was encapsulated within the apo horse spleen ferritin (AFt) nanocage, and the X-ray structure of the drug-loaded protein was refined at 1.49 Å resolution. Two Pt binding sites, different from the one observed in the cisplatin-encapsulated AFt, were identified in Ft subunits by inspection of anomalous electron density maps at two wavelengths and difference Fourier electron density maps, which provide the necessary sensitivity to discriminate between Pt from CBDCA and Cd ions that are present in the crystallization conditions. Pt centers coordinate to the NE2 atom of His49 and to the NE2 atom of His132, both on the inner surface of the Ft nanocage.
第二代铂类抗癌药物卡铂（CBDCA）被包裹在脱铁马脾铁蛋白（AFt）纳米笼中，载药蛋白的X射线结构在1.49 Å分辨率下得到优化。通过在两个波长下检查反常电子密度图和差分傅里叶电子密度图，在Ft亚基中确定了两个与包裹顺铂的AFt中观察到的不同的铂结合位点，这些图提供了区分CBDCA中的铂和结晶条件中存在的镉离子所需的灵敏度。铂中心与Ft纳米笼内表面的His49的NE2原子和His132的NE2原子配位。
