- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Electron Spin Resonance Studies
- Click Chemistry and Applications
- Solid-state spectroscopy and crystallography
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Molecular Sensors and Ion Detection
- Photochromic and Fluorescence Chemistry
- Advanced MRI Techniques and Applications
- Molecular Junctions and Nanostructures
- RNA modifications and cancer
- Antimicrobial Peptides and Activities
- Nanoplatforms for cancer theranostics
- Atomic and Subatomic Physics Research
- Lanthanide and Transition Metal Complexes
- Supramolecular Self-Assembly in Materials
- Enzyme Structure and Function
- Virus-based gene therapy research
The University of Tokyo
2016-2025
Bunkyo University
2019-2021
Japan Science and Technology Agency
2011-2015
Kyushu University
2002-2015
Graduate School USA
2015
Centre de Recherche en Économie et Statistique
2014
Centre for Research in Engineering Surface Technology
2014
Center for Responsible Travel
2014
Aomori University
2011-2013
Kyoto University
2002-2012
The lipophilic CdSe quantum dot (QD) coated with trioctylphosphine oxide (TOPOQD) can be extracted from chloroform into water upon interaction macrocyclic glycocluster amphiphile 1. QD-conjugated and highly fluorescent sugar ball of a size 15 nm (TOPOQD1) thus solubilized in readily invades Hela cells via endocytosis. endocytic activity TOPOQD1 (15 nm), light those the micellar homoaggregate 1 (5 nm) virus-like 1−DNA conjugate (50 as references, reveals dramatic effect ≫ 5) subviral region....
Number- and size-controlled macromolecular associations are common in biology with viruses as a typical example. We report here novel example of artificial viruses, which the double-helical DNA is coated 4-nm sized neutral glycocluster nanoparticles (GNPs) coating stoichiometry ∼2 GNPs per helical pitch (10 base pairs), where GNP arises from micellization cone-shaped, quadruple-chain amphiphile having eight saccharide moieties β-glucoside termini on calix[4]resorcarene macrocycle. The...
Abstract Oligonucleotide‐based hepatocyte growth factor (HGF) mimetics are described. A DNA aptamer to Met, a cognate receptor for HGF, was shown induce Met activation when used in dimer form. The most potent dimer, ss‐0, which composed solely of 100‐mer single‐stranded DNA, exhibited nanomolar potency. Aptamer ss‐0 reproduced HGF‐induced cellular behaviors, including migration and proliferation. present work sheds light on oligonucleotides as novel chemical entity the design mimetics.
A fluorescent aptamer sensor was applied to the analysis of extracellular chemical transmitter dynamics. We utilized a tocopherol-labeled aptamer, which allowed direct anchoring on cell surface while retaining its performance as sensor. The fast-responsive DNA sensor, targets adenine compounds, anchored brain astrocytes. Fluorescence imaging aptamer-anchored astrocytes enabled real-time monitoring release compounds gliotransmitter, synchronized with calcium wave propagation in neighboring cells.
The HGF/c-Met pathway is known to play a key role in cancer metastasis. CLN0003_SL1, 50-mer DNA aptamer that binds the c-Met protein, was found inhibit HGF-induced activation. This could suppress cell motility vitro.
The reprogramming of receptor-ligand interactions affords an opportunity to direct cells respond user-defined external cues. Although this has often been achieved via the genetic engineering receptors, alternative, nongenetic approach is highly demanded. In article, we propose design oligonucleotide-based synthetic switches that feature ability reprogram ligand specificity growth factor receptor. We demonstrated our induced signaling formation dynamic complex with specific cues would...
Naturally occurring peptides with high membrane permeability often have ester bonds on their backbones. However, the impact of amide-to-ester substitutions has not been directly evaluated. Here we report effect and conformational ensemble cyclic related to permeation. Amide-to-ester are shown improve dipeptides a model hexapeptide. NMR-based analysis enhanced sampling molecular dynamics simulations suggest that transition hexapeptide upon permeation is differently influenced by an...
We here report a novel example of artificial glycoviral vectors constructed via number- and size-controlled gene (pCMVluc, 7040 bp) coating with micellar glycocluster nanoparticles (GNPs) calix[4]resorcarene-based macrocyclic amphiphiles having eight or five saccharide moieties terminal alpha-glucose (alpha-Glc), beta-glucose (beta-Glc), beta-galactose (beta-Gal) residues. The resulting glycoviruses are compactly packed (approximately 50 nm) well charge-shielded (zeta approximately equal 0...
2-Acylamino-1,8-naphthyridine (1), which possesses hydrogen bonding groups fully complementary to guanine (G), selectively binds a single G bulge of duplex DNA. The melting temperature (Tm) the containing was increased by presence 1, whereas no increase Tm observed for duplexes adenine (A) and thymine (T) bulges as well normal duplex. Riboflavin-sensitized photooxidation DNA GG steps opposite A inhibited 1 at bulge. DNase I footprinting titration indicated selective binding with an...
Hyperpolarization is a highly promising technique for improving the sensitivity of magnetic resonance chemical probes. Here we report [15N, D9]trimethylphenylammonium as platform designing variety hyperpolarized The structure shows remarkably long 15N spin–lattice relaxation value (816 s, 14.1 T) retaining its spin state. extended lifetime enables detection signal several tens minutes and thus overcomes intrinsic short analysis time Versatility demonstrated by applying it to three types...
A 76-mer single-stranded DNA acts as functional mimic of basic fibroblast growth factor (bFGF), one the essential factors for stem cell culture.
Although growth factors have great therapeutic potential because of their regenerative functions, they often intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides recently emerged promising chemical entities for designing synthetic alternatives to factors. However, applications in vivo been recognized a challenge susceptibility nucleases limited distribution target tissue. Here, we present the first example oligonucleotide-based factor mimetics that...
There is a growing demand for structure determination from small crystals, and the three-dimensional electron diffraction (3D ED) technique can be employed this purpose. However, 3D ED has certain limitations related to crystal thickness data quality. We here present application of serial X-ray crystallography (SX) with free lasers (XFELs) (a few μm or less) thin hundred nm crystals novel compounds dispersed on substrate. For XFEL exposures, two-dimensional (2D) scanning substrate coupled...
We report on the application of a new class oligonucleotide reporter probes, QUAL that "light up" when nucleophilic phosphorothioate probe binds adjacent to dabsyl-quenched probe. These self-ligating DNA probes were used for sequence-specific detection 16S rRNA in Escherichia coli cells. Strong fluorescence was observed only and quenched dabsyl bind side-by-side target. The results demonstrate use detect specific RNA sequences bacterial cells without enzymes washing steps.
Dimeric 2-amino-1,8-naphthyridine selectively binds to a G−G mismatch with high affinity (Kd = 53 nM). We have investigated binding mechanism of naphthyridine dimer 2 by spectroscopic studies, thermodynamic analysis, and structure−activity studies for the thermal stabilization mismatch. 1H NMR spectra complex 9-mer duplex d(CATCGGATG)2 containing showed that all hydrogens in two rings were observed upfield compared those free state. The 2D-NOESY experiments each guanine within π-stack. In CD...
We describe the synthesis and study of multicolor quenched autoligating (QUAL) probes for identification discrimination closely related RNA DNA sequences in solution bacteria. In these probes, a dabsyl quencher doubles as an activator oligonucleotide-joining reaction. The oligonucleotides remain dark until they bind at adjacent sites, "light up" on nucleophilic displacement probe by phosphorothioate probe. Four fluorescent dye conjugates were prepared tested with targets that differ one...
A newly designed target-assisted self-cleavage (TASC) probe composed of a target-binding site and DNAzyme domain undergoes TASC when activated via hybridization with target DNA/RNA. This self-splicing or self-dissociation reaction occurs in catalytic manner the as substrate catalyst, since fragmented products are automatically released from target, thus amplifying sequence information latter under non-PCR, i.e., isothermal enzyme/reagent-free, conditions. fluorescence-reporting having...
We describe a new fluorescence reporting strategy in which dabsyl, well-known quencher, activates hydroxyl group probe to convert it leaving group. When nucleophilic phosphorothioate binds adjacent dabsyl quenched probe, autoligation occurs, releasing the and lighting up probes, This signal change can be used detect single nucleotide differences DNA without enzymes or reagents.
The “light-up” RNA aptamer–Hoechst pair can be used as a fluorescent tag to monitor transcription processes.
We have designed a strategy to generate light-up fluorophore-aptamer pair based on down-modification of conventional DNA-staining dye suppress its affinity the original dsDNA targets, followed by reselection aptamers that would bind modified dye. Following this line, we prepared micropolarity-sensitive Hoechst derivative possessing two tBu groups with low usual AT-rich targets. DNA selected in vitro from random pool worked as triggers enhance fluorescence an otherwise nonfluorescent...
Elucidation of biological phenomena requires imaging microenvironments in vivo. Although the seamless visualization vivo hypoxia from level whole-body to single-cell has great potential discover unknown and medical fields, no methodology for achieving it been established thus far. Here, we report whole-organ hypoxia, an important microenvironment, at resolution using activatable covalent fluorescent probes compatible with tissue clearing. We initially focused on overcoming incompatibility...
Structure-guided design led to the discovery of a small and potent peptide inhibitor measles virus fusion protein.