X-ray Structure of the Carboplatin-Loaded Apo-Ferritin Nanocage

Nicola Pontillo, Giarita Ferraro, John R. Helliwell, Angela Amoresano, Antonello Merlino

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)433-437
    Number of pages5
    JournalACS Medicinal Chemistry Letters
    Volume8
    Issue number4
    Early online date28 Feb 2017
    DOIs
    Publication statusPublished - 13 Apr 2017

    Keywords

    • carboplatin
    • encapsulated drugs
    • ferritin
    • Pt-based drugs

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