Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs, which, in contrast to hydroxyferrocifen, after activation form not only quinone methides (QMs), but also catalysts (iron or ferrocenium ions). The released products act in a concerted fashion. In particular, QMs alkylate glutathione, thereby inhibiting the antioxidative system of the cell, whereas the iron species induce catalytic generation of hydroxyl radicals. Since the catalysts are formed as products of the activation reaction, it proceeds autocatalytically. The most potent prodrug described here is toxic toward cancer cells (human promyelocytic leukemia (HL-60), IC(50) = 9 μM, and human glioblastoma-astrocytoma (U373), IC(50) = 25 μM), but not toxic (up to 100 μM) toward representative nonmalignant cells (fibroblasts).
DNA sequences can hybridize with each other in a predictable and a programmable manner to form linear and branched double-stranded (ds) helical structures. This ability makes DNA an excellent building block for preparation of nanostructures of defined shapes and sizes. For example, surface patterns and complex 2D and even 3D objects have been obtained by self-assembly of DNA strands.[1] To make dsDNA conductive, it has been coated with metals, metal oxides, or metal sulfides. For example, a number of methods for the complete coverage of DNA with Au 0 , Pd 0 , Pt 0 , Ag 0 , Cu 0 , and CdS have been reported. [2,3] However, less is known about the controlled modification of pre-selected sections of DNA. The first example of the selective coating of DNA with metal was reported by Braun and co-workers.[4] In particular, they protected a portion of l DNA with a RecA protein/ ssDNA complex. This step was followed by metallization of the unprotected DNA by sequential reduction of Ag + and Au 3+ . Finally, the RecA protein was degraded, exposing the protected region of l DNA for further manipulations. This method provided two stretches of conducting DNA wires that are interrupted by a circa 1 mm-long stretch of nonconductive DNA. However, as RecA-induced homologous recombination is efficient only with long DNA sections, this approach is limited to construction of rather large molecular objects (>1 mm).Chemical synthesis of dsDNA containing metal ions between coordinating base pairs has been reported. [5] By the variation of the number of such base pairs, the length of the metal-containing stretches within the DNA can be varied.[5] It still remains to be experimentally confirmed that the metal ion/DNA complexes obtained are conductive and, therefore, applicable as conducting wires.Herein we describe a method for selective metallization of ds regions of DNA with copper(0) (Figure 1). ssDNA overhangs present in the duplexes could potentially be used as addressable anchors for preparation of functional devices based on metallized dsDNA. We prepared a simple device of this type containing two metallized dsDNA connected by a non-metallized rigid linker.
A fluorogenic, nucleic acid directed, Cu(+)-catalyzed chemical reaction was developed that allows sequence-specific detection of nucleic acids at concentrations as low as 20 nM through monitoring of the increase of the fluorescence intensity. A single nucleotide mismatch in the template strand leads to the complete inhibition of this reaction. We observed that a Cu(+) ion stabilized with a water-soluble ligand is a significantly more efficient catalyst than free Cu(+).
Wählerische Partikel: Eine Methode für die selektive Bildung von Kupfer‐Nanopartikeln an dsDNA‐Templaten wurde entwickelt. Die Größe der Nanopartikel kann über die Länge der dsDNA gesteuert werden, und einzelsträngige DNA wirkt nicht als Templat (siehe Schema). Einzelstrangüberhänge wurden genutzt, um eine Nanostruktur bestehend aus zwei metallisierten dsDNAs und einem nichtmetallisierten starren Linker aufzubauen.
The reaction of ester hydrolysis catalysed by a DNA duplex in a sequence specific fashion has been developed, which is the fastest and most high yielding in comparison with the known reactions of this type.
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