Merck
  • Home
  • Search Results
  • Molecular mass spectrometry in metallodrug development: a case of mapping transferrin-mediated transformations for a ruthenium(III) anticancer drug.

Molecular mass spectrometry in metallodrug development: a case of mapping transferrin-mediated transformations for a ruthenium(III) anticancer drug.

Analytica chimica acta (2014-12-03)
Maciej Jarosz, Magdalena Matczuk, Katarzyna Pawlak, Andrei R Timerbaev
ABSTRACT

Electrospray ionization mass spectrometry (ESI-MS) techniques have been used to characterize the speciation of a Ru(III) anticancer drug, indazolium trans-[tetrachloridobis(1H-indazole) ruthenate(III)], upon its binding to transferrin and the impact of cellular reducing components on drug-transferrin adducts. Using time-of-flight ESI-MS, the polymorphism of apo- (iron-free) and holo-form (iron-saturated) of the protein was confirmed. While the ruthenium moieties bound to each of five isoforms under simulated extracellular conditions are essentially identical in numbers for apo- and holo-transferrin, distinct differences were found in the composition of Ru(III) species attached to either of the protein forms, which are dominated by differently coordinated aquated complexes. On the other hand, at least one of the RuN bonds in metal-organic framework remains intact even after prolonged interaction with the protein. Triple quadrupole tandem ESI-MS measurements demonstrated that the ruthenium species released from drug adducts with holo-transferrin in simulated cancer cytosol are underwent strong ligand exchange (as compared to the protein-bound forms) but most strikingly, they contain the metal center in the reduced Ru(II) state. In vitro probing the extra- and intracellular interactions of promising Ru(III) drug candidate performed by ESI-MS is thought to shed light on the transportation to tumor cells by transferrin and on the activation to more reactive species by the reducing environment of solid tumors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Citric acid, 99%
Sigma-Aldrich
Citric acid, anhydrous, suitable for cell culture, suitable for plant cell culture
Sigma-Aldrich
L-Glutathione reduced, ≥98.0%
Sigma-Aldrich
L-Glutathione reduced, BioXtra, ≥98.0%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Citric acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Citric acid, ACS reagent, ≥99.5%
Supelco
Acetonitrile, analytical standard
Sigma-Aldrich
L-Glutathione reduced, suitable for cell culture, BioReagent, ≥98.0%, powder
Supelco
Ammonium ion solution for ISE, 1000 mg/kg N, analytical standard (for ion-selective electrodes)
Sigma-Aldrich
Citric acid, BioUltra, anhydrous, ≥99.5% (T)
Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard
Ascorbic acid, European Pharmacopoeia (EP) Reference Standard
Millipore
Bifido Selective Supplement B, suitable for microbiology
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Ammonium-14N chloride, 99.99 atom % 14N, 15N-depleted, 99% (CP)
Sigma-Aldrich
2-Hydroxybutyric acid sodium salt, 97%
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Ultrapure Acetonitrile, for DNA synthesis
Supelco
Ascorbic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Acetonitrile
Sigma-Aldrich
Ultrapure Acetonitrile
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Citric acid, certified reference material, TraceCERT®
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, for HPLC, for UV, ≥99.9% (GC)