Cellular uptake of metallated cobalamins.

Tran MT; Stürup S; Lambert IH; Gammelgaard B; Furger E; Alberto R

doi:10.1039/c5mt00272a

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Journal article

Cellular uptake of metallated cobalamins.

Tran MT Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. ariel@aci.uzh.ch.
Stürup S Department of Pharmacy, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. stefan.sturup@sund.ku.dk.
Lambert IH Department of Biology, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark.
Gammelgaard B Department of Pharmacy, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. stefan.sturup@sund.ku.dk.
Furger E Center for Radiopharmaceutical Science, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland.
Alberto R Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. ariel@aci.uzh.ch.

2016-01-08

Published in:

Metallomics : integrated biometal science. - 2016

Proton Magnetic Resonance Spectroscopy

English Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12.

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