Cellular effects of transferrin coordinated to.
Estimates of the net equilibrium binding constants for [(H2O)(NH3)5RuII]2+, [Cl(NH3)5RuIII]2+, cis-[(H2O)2(NH3)4RuII]2+ and cis-[Cl2(NH3)4RuIII]+ with apotransferrin (Tf) and holotransferrin (Fe2Tf) suggests that RuIII, but not RuII complexes bind with a higher affinity to the iron binding sites. Several other presumably histidyl imidazole sites bind with approximately the same affinity (Keff = 10(2) to 10(3) M(-1) to both RuII and RuIII. Compared to HeLa cells, an order of magnitude higher level of nuclear DNA binding ([Ru]DNA/[P]DNA) was required to achieve the same level of toxicity in Jurkat Tag cells, which probably relates to the substantially higher levels of cis-[Cl2(NH3)4Ru]+ needed to inhibit 50% of the cell growth in the Jurkat Tag cell line. Against Jurkat Tag cells, the toxicity of the pentaammineruthenium(III) group is enhanced by approximately two orders of magnitude upon binding primarily to the Fe-sites in apotransferrin, whereas the toxicity of the tetraammineruthenium(III) moiety is only marginally increased. Binding to Fe2Tf does not increase the toxicity of either group. Significant dissociation over 24 h of the ammineruthenium(III) ions from apotransferrin requires reduction to RuII.
Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
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Frasca
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Gehrig
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Clarke
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D019343:Citric Acid / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D010084:Oxidation-Reduction; D011485:Protein Binding; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014168:Transferrin / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017975:Ruthenium Compounds; D014168:Transferrin; D019343:Citric Acid; D004247:DNA; D005978:Glutathione