A Ruthenocene鈥揚NA Bioconjugate 鈥?Synthesis, Characterization, Cytotoxicity, and AAS-Detected Cellular Uptake

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• 作者：Annika Gross ; Nina H眉sken ; Julia Schur ; 艁ukasz Raszeja ; Ingo Ott ; Nils Metzler-Nolte
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：September 19, 2012
• 年：2012
• 卷：23
• 期：9
• 页码：1764-1774
• 全文大小：366K
• 年卷期：v.23,no.9(September 19, 2012)
• ISSN：1520-4812

文摘

Labeling of peptide nucleic acids (PNA) with metallocene complexes is explored herein for the modulation of the analytical characteristics, as well as biological properties of PNA. The synthesis of the first ruthenocene鈥揚NA conjugate with a dodecamer, mixed-sequence PNA is described, and its properties are compared to a ferrocene-labeled analogue as well as an acetylated, metal-free derivative. The synthetic characteristics, chemical stability, analytical and thermodynamic properties, and the interaction with cDNA were investigated. Furthermore, the cytotoxicity of the PNA conjugates is determined on HeLa, HepG2, and PT45 cell lines. Finally, the cellular uptake of the metal-containing PNAs was quantified by high-resolution continuum source atomic absorption spectrometry (HR-CS AAS). An unexpectedly high cellular uptake to final concentrations of 4.2 mM was observed upon incubation with 50 渭M solutions of the ruthenocene鈥揚NA conjugate. The ruthenocene label was shown to be an excellent label in all respects, which is also more stable than its ferrocene analogue. Because of its high stability, low toxicity, and the lack of a natural background of ruthenium, it is an ideal choice for bioanalytical purposes and possible medicinal and biological applications like, e.g., the development of gene-targeted drugs.