RESUMEN
Identifying positions at which anticancer drug molecules incorporate into DNA is essential to define mechanisms underlying their activity, but current methodologies cannot yet achieve this. The thymidine fluorine substitution product trifluridine (FTD) is a DNA-damaging anticancer agent thought to incorporate into thymine positions in DNA. This mechanism, however, has not been directly confirmed. Here, we report a means to detect FTD in a single-stranded oligonucleotide using a method to distinguish single molecules by differences in electrical conductance. Entire sequences of 21-base single-stranded DNAs with and without incorporated drug were determined based on single-molecule conductances of the drug and four deoxynucleosides, the first direct observation of its kind. This methodology may foster rapid development of more effective anticancer drugs.
Asunto(s)
Antineoplásicos/química , ADN/química , Análisis de Secuencia de ADN/métodos , Algoritmos , Antineoplásicos/farmacología , ADN/metabolismo , Humanos , Teoría Cuántica , Análisis de Secuencia de ADN/instrumentación , Procesamiento de Señales Asistido por Computador , Trifluridina/química , Trifluridina/farmacología , Agua/químicaRESUMEN
Single-molecule junctions are of particular interest in molecular electronics. To realize molecular electronic devices, it is crucial that functional single-molecule junctions are connected to each other by using joint units on the atomic scale. However, good joint units have not been reported because controlling the charge transport directions through the junctions is not trivial. Here, we report a joint unit that controls and changes the charge transport directions through the junctions, by using a ruthenium-tris-bipyridine (RuBpy) complex. The RuBpy single-molecule junction was fabricated with scanning tunnelling microscopy-based break junction techniques. The RuBpy single-molecule junction showed two distinct high and low conductance states. The two states were characterized by the conductance measurement, the correlation analysis, and the comparative experiment of bipyridine (Bpy), which is the ligand unit of RuBpy. We demonstrate that the Ru complex has multiple charge transport paths, where the charge is carried vertically and horizontally through the complex depending on the path.
