title: A ruthenocene-PNA bioconjugate--synthesis, characterization, cytotoxicity, and AAS-detected cellular uptake.
abstract: 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-PNA 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 μM solutions of the ruthenocene-PNA 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.
authors: Inorganic Chemistry I, Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, D-44801 Bochum, Germany.
authors: Annika
authors: A
authors: Gross
authors: Nina
authors: N
authors: Hüsken
authors: Julia
authors: J
authors: Schur
authors: Łukasz
authors: Ł
authors: Raszeja
authors: Ingo
authors: I
authors: Ott
authors: Nils
authors: N
authors: Metzler-Nolte
mesh_terms: D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013054:Spectrophotometry, Atomic / Q000379:methods*
chemical_list: D009942:Organometallic Compounds; D020135:Peptide Nucleic Acids; C016721:ruthenocene