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

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

doi:10.1021/acsmedchemlett.7b00025

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

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

^*Corresponding author for this work

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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 language	English
Pages (from-to)	433-437
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	8
Issue number	4
Early online date	28 Feb 2017
DOIs	https://doi.org/10.1021/acsmedchemlett.7b00025
Publication status	Published - 13 Apr 2017

Keywords

carboplatin
encapsulated drugs
ferritin
Pt-based drugs

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsmedchemlett.7b00025

manuscriptACSMEDCHEMLET_revisedAccepted author manuscript, 473 KB

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title = "X-ray Structure of the Carboplatin-Loaded Apo-Ferritin Nanocage",

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 {\AA} 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.",

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T1 - X-ray Structure of the Carboplatin-Loaded Apo-Ferritin Nanocage

AU - Pontillo, Nicola

AU - Ferraro, Giarita

AU - Helliwell, John R.

AU - Amoresano, Angela

AU - Merlino, Antonello

PY - 2017/4/13

Y1 - 2017/4/13

N2 - 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.

AB - 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.

KW - carboplatin

KW - encapsulated drugs

KW - ferritin

KW - Pt-based drugs

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U2 - 10.1021/acsmedchemlett.7b00025

DO - 10.1021/acsmedchemlett.7b00025

M3 - Article

AN - SCOPUS:85017529182

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SP - 433

EP - 437

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 4

ER -

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

Abstract

Keywords

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