A5046658611- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- Molecular Junctions and Nanostructures
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Fibroblast Growth Factor Research
- Photochromic and Fluorescence Chemistry
- Nanopore and Nanochannel Transport Studies
- Liver physiology and pathology
- Dendrimers and Hyperbranched Polymers
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Advanced MRI Techniques and Applications
- Quantum-Dot Cellular Automata
- Carbohydrate Chemistry and Synthesis
- Intestinal Malrotation and Obstruction Disorders
- Antimicrobial Peptides and Activities
- Genomics and Chromatin Dynamics
- Circadian rhythm and melatonin
- Lanthanide and Transition Metal Complexes
- Hernia repair and management
- Gene Regulatory Network Analysis
- Electrochemical sensors and biosensors
The University of Tokyo
2015-2025
Bunkyo University
2021
Graduate School USA
2020
Kyushu University
2011-2014
Aomori University
2014
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.
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...
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...
Zwitterionic polymer PMPC was conjugated to a DNA aptamer enhance its therapeutic efficacy in vivo , while minimizing the recognition by anti-PEG antibodies.
Receptor tyrosine kinases (RTKs) play a pivotal role in cell signaling through their activation via dimerization. Recent studies have demonstrated the importance of temporal dynamics RTK activity and downstream signals, such as ERK, determining fate. To better understand these dynamics, it is essential to develop methods capable controlling with high resolution. However, techniques for precisely modulating endogenous RTKs without requiring genetic modification remain insufficiently...
Monoamine oxidase (MAO) A is a flavoenzyme that catalyzes the oxidation of biologically important monoamines and thought to be associated with psychiatric disorders. Here, we report strategy for rationally designing 19F magnetic resonance imaging probe specific detection human MAO-A (hMAO-A) activity. Our designed was oxidized expeditiously by hMAO-A produce 2-fluoro-4-nitrophenol via spontaneous β-elimination mechanism. Concomitant structural change product, chemical shift changed 4.2 ppm,...
We developed a dendritic molecular glue PCGlue-NBD that can serve universally to "turn on" protein–protein interactions (PPIs) spatiotemporally. carrying multiple guanidinium ion (Gu+) pendants adhere strongly target proteins and cover their surfaces including the PPI interface regions, thereby suppressing PPIs with receptor proteins. Upon irradiation UV light, on protein is photocleaved at butyrate-substituted nitroveratryloxycarbonyl linkages in dendrimer framework, so multivalency for...
Quantum-tunneling-based DNA sequencing is a single molecular technology that has great potential for achieving facile and high-throughput sequencing. In principle, the sequence of could be read out by time trace tunnel current can changed according to conductance nucleobases passing through nanosized gap electrodes. However, efficient base-calling four genetic alphabets been seriously impeded due similarity among canonical nucleotides. this article, we demonstrate replacement...
Designing synthetic surrogates of functional proteins is an important, albeit challenging, task in the field chemistry. A strategy toward design agonists for growth factor or cytokine receptors that elicit a desired signal activity has been high demand, as such ligands hold great promise safer and more effective therapeutics. In present study, we used DNA aptamer building block described strategy-guided receptor agonist with fine-tuned agonism. The developed partial can regulate...
We demonstrated the nongenetic temporal control of cell signaling using a DNA-based synthetic surrogate growth factor.
Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing significant hindrance to postsurgical recovery. Although several strategies have been developed alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied therapeutic effect mechanism our recently thermally stable oligonucleotide-based mimetics hepatocyte growth factor (HGF DNA aptamer) PPA. The HGF aptamer effectively inhibited canonical TGF-β1...
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.
Cell membrane receptors regulate cellular responses through sensing extracellular environmental signals and subsequently transducing them. Receptor engineering provides a means of directing cells to react designated external cue exert programmed functions. However, rational design precise modulation receptor signaling activity remain challenging. Here, we report an aptamer-based signal transduction system its applications in controlling customizing the functions engineered receptors. A...
We developed a photoreactive molecular glue, BPGlue-N3, which can provide universal strategy to enhance the efficacy of DNA aptamers by temporary-to-permanent stepwise stabilization their conjugates with target proteins. As proof-of-concept study, we applied BPGlue-N3 SL1 (DNA aptamer)/c-Met (target protein) conjugate system. adhere and temporarily stabilize this aptamer/protein multivalently using its guanidinium ion (Gu+) pendants that form salt bridge oxyanionic moieties (e.g.,...
Dopamine (DA) is a monoamine neurotransmitter that plays important roles in the brain, and whose levels brain are associated with several neurological psychiatric disorders. Therefore, DA metabolism inhibitors have been used as therapeutic agents. Here, we report 1H NMR probe for situ analysis of metabolism, its application to inhibitor screening. We designed doubly 13C-labeled (13C2-DA) probe. The combination 13C2-DA 1H–{13C–13C′} technique allowed selective thus monitoring metabolism....
Growth factor receptors are activated through dimerization by the binding of their ligands and play pivotal roles in normal cell function. However, aberrant activity has been associated with cancer malignancy. One main causes receptor activation is overexpression resultant formation unliganded dimers, which can be absence external ligand molecules. Thus, dimer a promising target to inhibit signaling cancer. Here, we report an aptamer that specifically binds fibroblast growth 2b inhibits...
[8-13C-7-15N]-labelled theophylline was synthesized and applied for in situ analysis using a 1H–{13C–15N} triple resonance NMR technique. The enabled selective detection of labelled mixture containing excess amino acids or crude mouse liver extract, where conventional 1H suffers from difficulty because background signals.
Artificial ligands that recognize membrane receptors with high affinity and specificity provide a means for the precise control of receptor activity resulting biological functions. In present work, we focused on previously reported DNA aptamer is functional mimic fibroblast growth factor (FGF) evaluated its specificity. It was revealed works as selective agonist FGF (FGFR) 1 owing to toward receptor, despite sequence homology in extracellular domains FGFR family. The excellent receptor-type...
Abstract Designing synthetic surrogates of functional proteins is an important, albeit challenging, task in the field chemistry. A strategy toward design agonists for growth factor or cytokine receptors that elicit a desired signal activity has been high demand, as such ligands hold great promise safer and more effective therapeutics. In present study, we used DNA aptamer building block described strategy‐guided receptor agonist with fine‐tuned agonism. The developed partial can regulate...
The pH-responsive DNA aptamer switch selectively inhibits the migration of cancer cells.