A5087565134- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Metal-Catalyzed Oxygenation Mechanisms
- Pharmacogenetics and Drug Metabolism
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Asymmetric Hydrogenation and Catalysis
- Microbial Natural Products and Biosynthesis
- Cancer Treatment and Pharmacology
- Enzyme Catalysis and Immobilization
- Genetic Neurodegenerative Diseases
- Biochemical and Structural Characterization
- Cancer, Hypoxia, and Metabolism
- Innovative Microfluidic and Catalytic Techniques Innovation
- Economic theories and models
- Stochastic processes and financial applications
- Nuclear Structure and Function
- Biochemical and Molecular Research
- Complex Systems and Time Series Analysis
- Muscle Physiology and Disorders
- Metal complexes synthesis and properties
- Bacteriophages and microbial interactions
- Porphyrin Metabolism and Disorders
Nagoya University
2018-2024
Graduate School USA
2018-2020
The University of Tokyo
2005-2015
University of Tsukuba
2013-2015
The University of Texas Southwestern Medical Center
2013-2015
Center for High Pressure Science and Technology Advanced Research
2012
University of Turku
2010
Aoyama Gakuin University
2003
Abstract Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic deficit. However, the molecular basis for toxicity toward function as modifiers remains unidentified. Here we show that impede ability to RBPs. Isothermal titration calorimetry size-exclusion chromatography revealed...
ConspectusBacterial cytochrome P450s (P450s) are at the focus of attention as potential biocatalysts for applications in green synthetic chemistry, they possess high activity hydroxylation inert substrate C–H bonds. The bacterial P450s, such P450BM3, is chiefly due to their specificity, and consequently, catalytic P450BM3 toward non-native substrates very low, limiting utility biocatalysts. To enable oxidation by without any mutagenesis, we have developed a series "decoy molecules", dummy...
Biological methane oxidation is a highly desirable method for the conversion of natural gas into liquid to meet increasing demand fuel and chemical feedstock as well reducing potent greenhouse effects emissions. Because hemoenzymes that can catalyze methanol have not been found, it has long considered hemoenzymes, including cytochrome P450s (P450s), cannot oxidative methane. Herein, we report catalytic by wild-type P450BM3, without any mutagenesis, in presence chemically evolved dummy...
Single-stranded silencing RNAs (ss-siRNAs) provide an alternative approach to gene silencing. ss-siRNAs combine the simplicity and favorable biodistribution of antisense oligonucleotides with robust through RNA interference (RNAi). Previous studies reported potent allele-selective inhibition human huntingtin expression by that target expanded CAG repeats within mutant allele. Mutant ataxin-3, genetic cause Machado–Joseph Disease, also contains repeat. We demonstrate here are inhibitors...
Highly effective dipeptidic decoy molecules, which stimulate the direct hydroxylation of benzene by wild-type cytochrome P450BM3, were successfully developed through a rationally designed screening method. Extensive synthesis and step-wise over 600 dipeptide derivatives performed for efficient evolution molecules. In presence N-(3-cyclopentyl)propanoyl-l-pipecolyl-l-phenylalanine (3CPPA-Pip-Phe), one most molecules discovered herein, catalytic turnover frequency total number reached 405...
Invasive binding event of PNA into DNA duplex was clearly observed both by atomic force microscope (AFM) imaging and electrophoretic mobility shift assay (EMSA) with the aid nanomechanical origami devices as 'single-molecule' visual probes, showing their potential universal platform for analysis invasion.
The self-sufficient cytochrome P450 102A1 (P450BM3), known for its highly efficient activation of molecular oxygen, was reconstituted with manganese protoporphyrin IX. This artificial enzyme (Mn-BM3) found to catalyze the monooxygenation various substrates by activating oxygen. Investigation using mechanistic probes (i.e., radical clock substrates) revealed that hydroxylation Mn-BM3 proceeds via a intermediate substrate, supporting involvement an "H atom abstraction/•OH recombination"...
By introducing an intercalator through D-threoninol to the 10–23 DNAzyme at junction between its catalytic loop and binding arm, RNA cleavage activity was greatly improved.
Mn-substituted full-length P450BM3 was constructed by transpeptidase Sortase A, showing catalytic hydroxylation of aliphatic C–H bonds with molecular oxygen.
Peptide nucleic acid (PNA) can form a stable duplex with DNA, and, accordingly, directly recognize double-stranded DNA through the formation of double-duplex invasion complex, wherein pair complementary PNA strands two PNA/DNA duplexes. Because does not require prior denaturation holds great potential for in cellulo or vivo applications. To broaden applicability invasion, we developed new conjugate ruthenium complex. This Ru-PNA exhibits higher DNA-binding affinity, which results enhanced...
Abstract Pseudo‐complementary peptide nucleic acid (pcPNA), as one of the most widely used synthetic DNA analogues, invades double‐stranded according to Watson–Crick rules form invasion complexes. This unique mode recognition induces structural changes at site and can be for a range applications. In this paper, pcPNA is conjugated with nuclear localization signal (NLS) peptide, its invading activity notably promoted both thermodynamically kinetically. Thus, double‐duplex complex formed...
Abstract A new type of high‐pressure reactor based on liquid‐flow pressurisation using a HPLC pump has been developed. This allows the easy and safe performance reactions with gaseous alkanes under high‐pressures up to 10 MPa (100 atm), without need for gas cylinders. The amount substrate required single reaction is very small compared conventional autoclave, which, when expensive gasses, such as 13 C‐labelled ethane, becomes critical. Employing this in conjunction cytochrome P450BM3...
A monophosphate group was attached to the terminus of pseudo-complementary peptide nucleic acid (pcPNA), and two thus modified pcPNAs were combined with Ce(IV)/EDTA for site-selective hydrolysis double-stranded DNA. The DNA scission notably accelerated by this chemical modification pcPNAs. These second-generation artificial restriction cutters (ARCUTs) differentiated target sequence so strictly that no occurred even when only one base-pair altered another. By using activated ARCUTs...
Unlocked nucleic acid (UNA) is an acyclic analogue of RNA that can be introduced into or DNA oligonucleotides. The increased flexibility conferred by the structure fundamentally affects strength base pairing, creating opportunities for improved applications and new insights molecular recognition. Here we test how UNA substitutions affect allele-selective inhibition expression trinucleotide repeat genes Huntingtin (HTT) Ataxin-3 (ATX-3). We find either combination mismatched bases alone...
Mutant huntingtin (HTT) protein is the cause of Huntington's disease (HD), an incurable neurological disorder. Almost all patients are heterozygous for mutant HTT and approaches that reduce levels while leaving expression wild-type intact might be ideal options therapeutic development. We have developed several allele-selective strategies silencing HTT, including single-stranded RNAs (ss-siRNAs). ss-siRNAs oligonucleotides containing chemical modifications permit action through RNA...
Abstract We have developed two novel approaches for the construction of artificial metalloenzymes showing either unique catalytic activities or substrate specificity. The first example is use a hollow cage apo-ferritin as reaction vessel hydrogenation olefins, Suzuki-Miyaura C-C coupling and phenylacetylene polymerization by employing Pd0 nano-clusters, Pd2+(η3-C3H5) complexes Rh1+(nbd) (nbd = norbornadiene) introduced in cage, respectively. second approach “decoy molecules” to change...
Peptide nucleic acid (PNA) is an analog of natural acids, where the sugar-phosphate backbone DNA replaced by electrostatically neutral N-(2-aminoethyl)glycine backbone. This unique peptide-based enables PNAs to form a very stable duplex with complementary acids via Watson–Crick base pairing since there no electrostatic repulsion between PNA and DNA·RNA. With this high affinity, have been used in wide range fields, from biological applications such as gene targeting, engineering probe sensor...
Oligodeoxyribonucleotide conjugates of ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) (EDTP) have been used to place a Ce(III)/EDTP complex in close proximity predetermined phosphodiester linkages complementary target oligonucleotide. In the presence atmospheric oxygen, Ce(III) is oxidized into Ce(IV) which, turn, efficiently cleaves linkage. No cleavage occurs at other single-stranded regions, which suggests that catalytic Ce species strictly localized next decrease reaction...
Artificial DNA cutters have been developed by us in our previous studies combining two strands of pseudo-complementary peptide nucleic acid (pcPNA) with Ce(IV)–EDTA-promoted hydrolysis. The pcPNAs modified nucleobases (2,6-diaminopurine and 2-thiouracil) instead conventional A T, can invade double-stranded to activate the target site for scission. This system has applied site-selective scissions plasmid, λ-phage, E. coli genomic DNA, human DNA. Here, we reported a still simpler more...
Oligonucleotides represent powerful DNA-recognition tools, but the formation of undesirable "self-duplexes" becomes more probable with increasing DNA affinity. Herein, we have developed a modified nucleobase "self-avoiding" properties. Facile methylation guanine yields cationic N7-methylguanine, which suppresses self-duplexes whilst improving affinity through electrostatic interaction.