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Cisplatin (cis-[PtCl2(NH3)2]) is a widely used chemotherapeutic that kills cancer cells by binding to DNA with its platinum(II) metal center. NAMI-A ((ImH)[trans-RuCl4(DMSO)(Im)]) was the first anti-cancer drug with a ruthenium(III) center to enter clinical trials; NAMI-A has improved action against metastasis and fewer side effects than cisplatin. These anti-cancer drugs are delivered intravenously, and a considerable amount of the drug binds to proteins in the bloodstream before reaching tumor cells. Interestingly, Ru(III) compounds are thought to mimic iron in the bloodstream by reversibly binding transferrin, an iron transport protein. This presents a promising method of drug delivery to tumors. On the other hand, Pt(II) compounds have been shown to have stronger, less reversible interactions with blood plasma proteins. A novel potential anticancer complex with both a Pt(II) center and a Ru(III) center was synthesized at Bard College, called IT127 ((Na/K)[Ru(III)Cl4(DMSO-S)(μ-pyz)Pt(II)(DMSO-S)Cl2]) . In this study, we sought to determine the binding reversibility of IT127 to transferrin as a potential mechanism of drug delivery to tumor cells. As a comparison, the binding reversibility of IT127 to human serum albumin (HSA) and NAMI-A to both transferrin and HSA was also examined. A method employing UV-visible spectrophotometry, gel filtration, and centrifugal filtration was developed to determine relative compound release from the plasma proteins after incubation of compound- protein adducts in conditions that disrupted non-covalent binding. Our preliminary results suggest that NAMI-A reversibly binds transferrin and irreversibly binds HSA, and that IT127 irreversibly binds both transferrin and HSA.
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Dooley, Katharine Elizabeth, "Reversibility of adduct formation between a potential anticancer platinum-ruthenium complex and blood plasma proteins" (2013). Senior Projects Spring 2013. 170.
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