ABSTRACT
Triplet repeat diseases are caused by the abnormal elongation of repeated sequences comprising three bases. In particular, the elongation of CAG/CTG repeat sequences is thought to result in conditions such as Huntington's disease and myotonic dystrophy type 1. Although the causes of these diseases are known, fundamental treatments have not been established, and specific drugs are expected to be developed. Pyrrole imidazole polyamide (PIP) is a class of molecules that binds to the minor groove of the DNA duplex in a sequence-specific manner; because of this property, it shows promise in drug discovery applications. Earlier, it was reported that PIP designed to bind CAG/CTG repeat sequences suppresses the genes that cause triplet repeat diseases. In this study, we performed an X-ray crystal structure analysis of a complex of double-stranded DNA containing A-A mismatched base pairs and a cyclic-PIP that binds specifically to CAG/CTG sequences. Furthermore, the validity and characteristics of this structure were analyzed using in silico molecular modeling, ab initio energy calculations, gel electrophoresis, and surface plasmon resonance. With our direct observation using atomic force microscopy and DNA origami, we revealed that the PIP caused structural changes in the DNA strands carrying the expanded CAG/CTG repeat. Overall, our study provides new insight into PIP from a structural perspective.
ABSTRACT
Herein, we report on the construction of Cu-histidine (His)-DNA hybrids as laccase-mimetic DNAzymes. Cu-His-DNAzymes showed remarkable activity in a colorimetric oxidation reaction between 2,4-dichlorophenol and 4-aminoantipyrine. Our results provide new insights for the systematic construction of tailor-made active sites for biomimetics.
Subject(s)
DNA, Catalytic , DNA, Catalytic/chemistry , Histidine/chemistry , Laccase/chemistry , Biomimetics , DNA/chemistry , Copper/chemistryABSTRACT
Fluorescent molecular rotors are versatile tools for the investigation of biomolecular interactions and the monitoring of microenvironmental changes in biological systems. They can transform invisible information into a fluorescence signal as a straightforward response. Their utility is synergistically amplified when they are merged with biomolecules. Despite the tremendous significance and superior programmability of nucleic acids, there are very few reports on the development of molecular rotor-type isomorphic nucleosides. Here, we report the synthesis and characterization of a highly emissive molecular rotor-containing thymine nucleoside (ThexT) and its 2'-O-methyluridine analogue (2'-OMe-ThexU) as fluorogenic microenvironment-sensitive sensors that emit vivid fluorescence via an interaction with the target proteins. ThexT and 2'-OMe-ThexU may potentially serve as robust probes for a broad range of applications, such as fluorescence mapping, to monitor viscosity changes and specific protein-binding interactions in biological systems.
