- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- HIV/AIDS drug development and treatment
- Asymmetric Hydrogenation and Catalysis
- Receptor Mechanisms and Signaling
- Influenza Virus Research Studies
- Glutathione Transferases and Polymorphisms
- Microbial Community Ecology and Physiology
- Colorectal Cancer Screening and Detection
- Photosynthetic Processes and Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Fluorine in Organic Chemistry
- HIV Research and Treatment
- Genomics, phytochemicals, and oxidative stress
- Synthesis and Characterization of Heterocyclic Compounds
- Chemical synthesis and alkaloids
- Synthesis and Catalytic Reactions
Nagoya University
1990-2025
Kyorin University
2024
Graduate School USA
2017-2019
Okayama University
2001-2018
The University of Tokyo
2008-2015
Japan Science and Technology Agency
2013-2015
Bunkyo University
2009-2013
Shibaura Institute of Technology
2013
Toyo Engineering (Japan)
2013
Information and Mathematical Science and Bioinformatics (Japan)
2006
Abstract Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported using liposomes or receptor‐ligands take several hours more to deliver oligonucleotides the cytoplasm due their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach 10 minutes after administration cultured cells. This rapid cytoplasmic internalization disulfide‐modified suggests existence an uptake pathway other than...
Starting with the clinical application of two vaccines in 2020, mRNA therapeutics are currently being investigated for a variety applications. Removing immunogenic uncapped from transcribed is critical research and Commonly used capping methods provide maximum efficiency around 80-90% widely Cap-0- Cap-1-type mRNAs. However, capped possesses almost identical physicochemical properties, posing challenges to their physical separation. In this work, we develop hydrophobic photocaged...
There are abundance of transcripts that code for no particular protein and remain functionally uncharacterized. Some these may have novel functions while others might be junk transcripts. Unfortunately, the experimental validation such to find functional non-coding RNA candidates is very costly. Therefore, our primary interest computationally mine candidate from a pool uncharacterized We introduce fRNAdb: database service hosts large collection including annotated/non-annotated sequences...
In pursuit of a better route: A new catalytic asymmetric synthesis Tamiflu was developed. The key transformation an Diels–Alder-type reaction 1 and 2 catalyzed by barium/F2-FujiCAPO complex in the presence CsF co-catalyst to construct core (see scheme; TMS=trimethylsilyl). product converted into 11 steps on gram scale.
We herein report the first covalent G-site-binding inhibitor for GST, GS-ESF (1), which irreversibly inhibited GSTP1-1 function. LC-MS/MS and X-ray structure analyses of covalently linked GST-inhibitor complex suggested that 1 reacted with Tyr108 GSTP1-1. The mechanism bond formation was discussed based on MD simulation results.
Abstract Messenger RNAs (mRNAs) with phosphorothioate modification (PS‐mRNA) to the phosphate site of A, G, C, and U all 16 possible combinations were prepared, translation reaction was evaluated using an E. coli cell‐free system. Protein synthesis from PS‐mRNA increased in 12 15 patterns when compared that unmodified mRNA. The protein yield 22‐fold at A/C sites introduced into region 5′‐end initiation codon. Single‐turnover analysis showed increases number translating ribosomes, thus...
Site-specific chemical modification of mRNA can improve its translational efficiency and stability. For this purpose, it is desirable to develop a complete synthesis method for chemically modified mRNA. The key reaction that introduces cap structure into the synthesized RNA. In study, we developed fast quantitative capping between 5′-phosphorylated RNA N7-methylated GDP imidazolide in presence 1-methylimidazole organic solvent dimethyl sulfoxide. It enabled preparation within 3 h. We...
A chiral polynuclear Gd complex derived from Gd(OiPr)3 and FujiCAPO (2 or 3) catalytically generated enolates through two distinct methods; transmetalation enol silyl ethers conjugate addition of cyanide to α,β-unsaturated N-acyl pyrroles. These can be enantioselectively protonated by a proton in an asymmetric environment the catalyst. Thus, catalytic enantioselective protonation was promoted catalyst (5−10 mol %) presence stoichiometric amount 2,6-dimethylphenol. Kinetic studies...
Abstract Messenger RNA (mRNA) has been implemented as COVID-19 vaccines. Following their success, the application of mRNA in cancer vaccines and protein replacement therapies is highly anticipated. The translational efficiency largely depends on cap structure located at its 5′ end. In particular, Cap-1 Cap-2 structures are known to exhibit higher synthesis levels than Cap-0 structure. Previously, we developed a method called PureCap technique, which utilizes reversed-phase high-performance...
Circular RNA without a stop codon enables rolling circle translation. we carried out one-pot chemical synthesis of circular from fragments. The synthesized RNAs acted as translation templates, despite the presence unnatural phosphoramidate linkages.
To study transcriptome dynamics without harming cells, it is essential to convert chemical bases. 4-Thiouridine (4sU) a biocompatible uridine analogue that can be converted into cytidine analogue. Although several reactions 4sU analogue, few studies have compared the features of these reactions. In this study, we performed three reported base conversion reactions, including osmium tetroxide, iodoacetamide, and sodium periodate treatment, as well new reaction using 2,4-dinitrofluorobenzene....
In this study, we systematically evaluated the efficacy of chemical modifications in enhancing translational activity and stability mRNA. We employed a primarily chemistry-based synthetic approach for modified mRNA, which is crucial position-specific introduction modifications, enabling an intricate detailed structure-activity relationship (SAR) hitherto unattainable with conventional methods. A pivotal innovation herein was 2´-F modification nucleosugar open reading framework (ORF) at...
CDAP is a useful reagent as an alternative to cyanogen bromide for the chemical ligation of DNA.
A copper(I)-catalyzed anomeric aminoalkynylation reaction of unprotected aldoses was realized. Use an electron-deficient phosphine ligand, boric acid to stabilize the iminium intermediate, and a protic additive (IPA) presumably enhance reversible carbohydrate–boron complexation were all essential for efficient conversion. The proceeded well even with natural disaccharide substrate, suggesting that developed catalytic could be useful synthesis glycoconjugates minimum use protecting groups.
Glutathione S-transferase π (GSTP1-1 ) is overexpressed in many types of cancer and involved drug resistance. Therefore, GSTP1-1 an important target therapy, GST inhibitors have been reported. We had previously developed irreversible inhibitor, GS-ESF, as effective inhibitor; however, its cellular permeability was too low for it to be used inhibiting intracellular GST. now new by introducing sulfonyl fluoride (SF) into chloronitrobenzene (CNB). The mechanism action revealed that CNBSF first...
Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities adolescents. The goal of this study was determine molecular mechanism responsible for these activities.We performed an vitro assay MAO-A, enzyme neurotransmitter degradation, using either active form - oseltamivir carboxylate (OC) or inactive prodrug ethyl ester (OEE). We also analysed docking MAO-A with OEE OC silico. Mouse behaviours...
We herein report a new approach for RNA interference, so-called "build-up RNAi" approach, where single-strand circular RNAs with photocleavable unit or disulfide moiety were used as siRNA precursors. The advantages of using these formats RNAi presented in aspects immunogenicity and cellular uptake.
We report on chemically modified PCR primers that enable the design of flexible sticky ends by introducing a photo-cleavable group at phosphate moiety. DNA fragments synthesized using these can be ligated with higher efficiency.
Abstract Post‐translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing and controlling their epigenetic are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind with substantial affinity. We report CA2 CA3, which exhibited sub‐micromolar affinity (especially trimethylated lysine). Multivalent display trisulfonated calix[4]arene was important for strong binding....
siRNA is a powerful method to suppress specific gene expression and has recently been utilized for molecular biology as well medicine. However, introduction of dsRNA stimulates immune-responses side-effects. In the present study, we N6-methyl adenosine, one natural modified nucleosides, instead adenosine in siRNA. When passenger or guide strand was completely replaced with immune response against evaded without any reduction RNAi activity. This knowledge will promote medical application...
Abstract Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported using liposomes or receptor‐ligands take several hours more to deliver oligonucleotides the cytoplasm due their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach 10 minutes after administration cultured cells. This rapid cytoplasmic internalization disulfide‐modified suggests existence an uptake pathway other than...
Auf der Suche nach einem besseren Weg: Bei einer neuen asymmetrischen Synthese von Tamiflu entsteht durch asymmetrische Diels-Alder-Reaktion 1 und 2 mit Barium-(F2-FujiCAPO)-Komplex als Katalysator CsF Cokatalysator das Ringsystem (TMS=Trimethylsilyl). Vom Produkt dieses Schritts aus war in 11 Stufen im Gramm-Maßstab zugänglich. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made...