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Cellular uptake of metallated cobalamins


Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger (2016). Cellular uptake of metallated cobalamins. Metallomics, 8(3):298-304.

Abstract

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-[PtIICl2(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.

Abstract

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-[PtIICl2(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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2016
Deposited On:12 Jan 2016 15:36
Last Modified:05 Apr 2016 19:52
Publisher:Royal Society of Chemistry
ISSN:1756-5901
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/C5MT00272A

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