title: Cellular uptake of metallated cobalamins.
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-[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.
authors.affiliation: Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. ariel@aci.uzh.ch.
authors.forename: Mai Thanh Quynh
authors.initials: MT
authors.lastname: Tran
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. stefan.sturup@sund.ku.dk.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.affiliation: Department of Biology, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark.
authors.forename: Ian Henry
authors.initials: IH
authors.lastname: Lambert
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. stefan.sturup@sund.ku.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
authors.affiliation: Center for Radiopharmaceutical Science, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Furger
authors.affiliation: Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland. ariel@aci.uzh.ch.
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008670:Metals / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy; D014805:Vitamin B 12 / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008670:Metals; D014805:Vitamin B 12