Solitary median maxillary central incisor syndrome caused by 22q11.2 microdeletion.

Solitary median maxillary central incisor (SMMCI) syndrome, the mildest form of the holoprosencephaly spectrum, is a rare anomaly characterized by the presence of a single midline central incisor in both the deciduous and permanent dentitions. Affected individuals can present with additional midline defects beyond dental findings. The 22q11.

Ligase-mediated synthesis of Cu-responsive allosteric DNAzyme with bifacial 5-carboxyuracil nucleobases.

A Cu-responsive allosteric DNAzyme has been developed by introducing bifacial 5-carboxyuracil (caU) nucleobases, which form both hydrogen-bonded caU-A and metal-mediated caU-Cu-caU base pairs. The base sequence was logically designed based on a known RNA-cleaving DNAzyme so that the caU-modified DNAzyme (caU-DNAzyme) can form a catalytically inactive structure containing three caU-A base pairs and an active form with three caU-Cu-caU pairs. The caU-DNAzyme was synthesized by joining short caU-containing fragments with a standard DNA ligase.

DNA three-way junction structures with amino acid side chains prepared via post-synthetic amide condensation.

DNA three-way junction (3WJ) structures with three amino acid side chains in the core have been synthesized post-synthetic DNA modification. Amide condensation reactions of oligonucleotides containing 2'-aminouridine with activated esters yielded DNA strands modified with His, Cys and Asp side chains to form modified 3WJs. Even a 3WJ with three negatively charged Asp side chains formed stably at room temperature.

Metal-dependent activity control of a compact-sized 8-17 DNAzyme based on metal-mediated unnatural base pairing.

A compact 8-17 DNAzyme was modified with a Cu-meditated artificial base pair to develop a metal-responsive allosteric DNAzyme. The base sequence was rationally designed based on the reported three-dimensional structure. The activity of the modified DNAzyme was enhanced 5.

Metal-mediated DNA strand displacement and molecular device operations based on base-pair switching of 5-hydroxyuracil nucleobases.

Rational design of self-assembled DNA nanostructures has become one of the fastest-growing research areas in molecular science. Particular attention is focused on the development of dynamic DNA nanodevices whose configuration and function are regulated by specific chemical inputs. Herein, we demonstrate the concept of metal-mediated base-pair switching to induce inter- and intramolecular DNA strand displacement in a metal-responsive manner.

Phenanthroline-modified DNA three-way junction structures stabilized by interstrand 3 : 1 metal complexation.

Incorporation of interstrand metal complexes into DNA is a versatile strategy for metal-dependent stabilization and structural induction of DNA supramolecular structures. In this study, we have synthesized DNA three-way junction (3WJ) structures modified with phenanthroline (phen) ligands. The phen-modified 3WJ was found to be thermally stabilized (Δ = +16.

Role of NKCC1 and KCC2 during hypoxia-induced neuronal swelling in the neonatal neocortex.

Neonatal hypoxia causes cytotoxic neuronal swelling by the entry of ions and water. Multiple water pathways have been implicated in neurons because these cells lack water channels, and their membrane has a low water permeability. NKCC1 and KCC2 are cation-chloride cotransporters (CCCs) involved in water movement in various cell types.

Cu-mediated DNA base pairing of a triazole-4-carboxylate nucleoside prepared by click chemistry.

Artificial metal-mediated DNA base pairing is a promising strategy for creating highly functionalized DNA supramolecules. Here we report a novel ligand-type triazole-4-carboxylate (TazC) nucleoside that is readily prepared by the click reaction. TazC nucleosides were found to form a stable TazC-Cu-TazC base pair inside DNA duplexes, resulting in Cu-specific duplex stabilization (Δ = +7.

Cu-mediated stabilisation of DNA duplexes bearing consecutive ethenoadenine lesions and its application to a metal-responsive DNAzyme.

Metal-mediated nucleobase pairing can play a central role in the expression of metal-responsive DNA functions. We report the Cu-mediated stabilisation of DNA duplexes bearing damaged nucleobases, 1,-ethenoadenine (εA), as metal-binding sites, which was utilised to construct a metal-responsive DNAzyme. Consecutive incorporation of three or more εA-εA mismatch pairs allowed for Cu-dependent significant duplex stabilisation through metal-mediated εA-Cu-εA base pairing.

Metal-mediated DNA base pairing of easily prepared 2-oxo-imidazole-4-carboxylate nucleotides.

Metal-mediated DNA base pairs, which consist of two ligand-type artificial nucleobases and a bridging metal ion, have attracted increasing attention in recent years as a different base pairing mode from natural base pairing. Metal-mediated base pairing has been extensively studied, not only for metal-dependent thermal stabilisation of duplexes, but also for metal assembly by DNA templates and construction of functional DNAs that can be controlled by metals. Here, we report the metal-mediated base paring properties of a novel 2-oxo-imidazole-4-carboxylate (Im) nucleobase and a previously reported 2-oxo-imidazole-4-carboxamide (Im) nucleobase, both of which can be easily derived from a commercially available uridine analogue.

Bipyridine-Modified DNA Three-Way Junctions with Amide Linkers: Metal-Dependent Structure Induction and Self-Sorting.

Invited for the cover of this issue are Yusuke Takezawa, Shiori Sakakibara, and Mitsuhiko Shionoya at The University of Tokyo. The image depicts the formation of stable DNA three-way junction structures crosslinked by an interstrand Ni (bpy) complex. Read the full text of the article at 10.

Bipyridine-Modified DNA Three-Way Junctions with Amide linkers: Metal-Dependent Structure Induction and Self-Sorting.

DNA three-way junction (3WJ) structures are essential building blocks for the construction of DNA nanoarchitectures. We have synthesized a bipyridine (bpy)-modified DNA 3WJ by using a newly designed bpy-modified nucleoside, U -3, in which a bpy ligand is tethered via a stable amide linker. The thermal stability of the bpy-modified 3WJ was greatly enhanced by the formation of an interstrand Ni (bpy) complex at the junction core (ΔT =+17.

Metal-responsive reversible binding of triplex-forming oligonucleotides with 5-hydroxyuracil nucleobases.

Metal-responsive triplex-forming oligonucleotides (TFOs) were synthesised by incorporating 5-hydroxyuracil (UOH) nucleobases as metal recognition sites. Binding of the UOH-containing TFO to the target natural DNA duplexes was reversibly regulated by the addition and removal of GdIII ions under isothermal conditions.

Site-specific polymerase incorporation of consecutive ligand-containing nucleotides for multiple metal-mediated base pairing.

An enzymatic method has been developed for the synthesis of DNA oligomers containing consecutive artificial ligand-type nucleotides. Three hydroxypyridone ligand-containing nucleotides forming Cu-mediated unnatural base pairs were continuously incorporated at a pre-specified position by a lesion-bypass Dpo4 polymerase. This enzymatic synthesis was applied to the development of a Cu-responsive DNAzyme.

Metal-Dependent DNA Base Pairing of 5-Carboxyuracil with Itself and All Four Canonical Nucleobases.

A 5-carboxyuracil (caU) nucleobase was found to pair not only with A (caU-A) by hydrogen bonding but also with other DNA nucleobases by metal coordination bonding. Metal-dependent formation of caU-Cu-caU, caU-Hg-T, caU-Ag-C, and caU-Cu-G pairs was demonstrated by duplex melting analysis and mass spectrometry. The duplexes containing caU-X (X = caU, T, C, and G) were significantly stabilized in the presence of the corresponding metal ions, while the DNA duplexes containing the caU-A pairs were destabilized by the addition of Cu.

Sharp Switching of DNAzyme Activity through the Formation of a Cu -Mediated Carboxyimidazole Base Pair.

DNAzymes are widely used as functional units for creating DNA-based sensors and devices. Switching of DNAzyme activity by external stimuli is of increasing interest. Herein we report a Cu -responsive DNAzyme rationally designed by incorporating one of the most stabilizing artificial metallo-base pairs, a Cu -mediated carboxyimidazole base pair (Im -Cu -Im ), into a known RNA-cleaving DNAzyme.

Allosteric Regulation of DNAzyme Activities through Intrastrand Transformation Induced by Cu(II)-Mediated Artificial Base Pairing.

Allosteric regulation is gaining increasing attention as a basis for the production of stimuli-responsive materials in many research areas including DNA nanotechnology. We expected that metal-mediated artificial base pairs, consisting of ligand-type nucleotides and a bridging metal ion, could serve as allosteric units that regulate the function of DNA molecules. In this study, we established a rational design strategy for developing Cu-responsive allosteric DNAzymes by incorporating artificial hydroxypyridone ligand-type nucleotides () that form a Cu-mediated base pair (-Cu-).

Supramolecular DNA Three-Way Junction Motifs With a Bridging Metal Center.

Various nano-sized supramolecular architectures have been constructed from DNA molecules via sequence-dependent self-assembly. A DNA three-way junction (3WJ), consisting of three oligonucleotides that are partially complementary to each other, is one of the simplest DNA supramolecular structures. This minireview covers studies on DNA 3WJ motifs bridged by an interstrand metal complex with some related works.

Phenotype-genotype correlations in patients with GNB1 gene variants, including the first three reported Japanese patients to exhibit spastic diplegia, dyskinetic quadriplegia, and infantile spasms.

We report the first three Japanese patients with missense variants in the GNB1 gene. Patients exhibited severe dyskinetic quadriplegia with cortical blindness and epileptic spasms, West syndrome (but with good outcomes), and hypotonic quadriplegia that later developed into spastic diplegia. Whole-exome sequencing revealed two recurrent GNB1 variants (p.

Enzymatic Synthesis of Cu(II)-Responsive Deoxyribozymes through Polymerase Incorporation of Artificial Ligand-Type Nucleotides.

Metal-mediated artificial base pairs, consisting of ligand-type nucleotides and a bridging metal ion, have shown promise as functional units to develop stimuli-responsive DNA materials. Although a variety of metal-mediated base pairs have been constructed with artificial ligand-type nucleotides and various metal ions, the application of such metal-mediated base pairs has been relatively poorly explored mainly due to the cumbersome chemical synthesis of artificial DNA strands. Herein we report a facile enzymatic method to synthesize DNA strands containing a ligand-type hydroxypyridone () nucleotide, which forms a Cu-mediated base pair (-Cu-).