A Ruthenocene–PNA Bioconjugate  Synthesis, Characterization, Cytotoxicity, and AAS-Detected Cellular Uptake

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

Additional file 2: Table S1. of Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury

Distribution of K8 and K18 variants in selected drug categories. (DOCX 44 kb

Additional file 1: Figure S1. of Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury

Identification of the novel variants (A) K8 K393R and (B) K18 D89H. A comparison with wild type (WT) sequences (left panels) reveals the heterozygous nature of the depicted variants. Standard single-letter amino acid abbreviations are used. (PDF 2587 kb