A5068707383- Parkinson's Disease Mechanisms and Treatments
- Organometallic Complex Synthesis and Catalysis
- Advanced Polymer Synthesis and Characterization
- Lanthanide and Transition Metal Complexes
- Prion Diseases and Protein Misfolding
- interferon and immune responses
- Alzheimer's disease research and treatments
- Trace Elements in Health
- Solid-state spectroscopy and crystallography
- Spectroscopy and Quantum Chemical Studies
- Fluorine in Organic Chemistry
- Influenza Virus Research Studies
- Advanced Chemical Physics Studies
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Machine Learning in Bioinformatics
- Neurological diseases and metabolism
- Amino Acid Enzymes and Metabolism
- Carbohydrate Chemistry and Synthesis
- Nonlinear Optical Materials Research
- Inflammasome and immune disorders
- Photorefractive and Nonlinear Optics
- Asymmetric Synthesis and Catalysis
Nagasaki University
2016-2024
Toho University Medical Center Sakura Hospital
2024
Toho University
2024
RIKEN
2019
Pioneer (Japan)
2019
RIKEN Advanced Science Institute
2014
Kyoto University
2011-2012
A perturbative extension to optimized coordinate vibrational self-consistent field (oc-VSCF) is proposed based on the quasi-degenerate perturbation theory (QDPT). scheme construct degenerate space (P space) developed, which incorporates configurations and alleviates divergence of expansion due localized coordinates in oc-VSCF (e.g., local O-H stretching modes water). An efficient configuration selection also implemented, screens out Hamiltonian matrix element between P (p) complementary Q...
Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms action is urgently required due to emergence viruses resistance currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which optimised for GPU-based supercomputer (DEstination Gpu Intensive MAchine; DEGIMA), by targeting influenza PA...
The hydrofluorination reaction of 3-bromooxindole using mild HF reagents in an ionic liquid is described. This transformation can operate at room temperature to give a series 3-substituted 3-fluorooxindole derivatives including racemic BMS 204352 (MaxiPost). mechanistic study about interactions between and 3-butyl-1-methylimidazolium tetrafluoroborate [bmim][BF4] also discussed on the basis energy calculations.
Prions are composed solely of the pathological isoform (PrPSc) normal cellular prion protein (PrPC). Identification different PrPSc structures is crucially important for understanding biology because pathogenic properties prions hypothesized to be encoded in PrPSc. However, these remain yet identified, incompatibility with conventional high-resolution structural analysis methods. Previously, we reported that region between first and second α-helix (H1∼H2) PrPC might cooperate more C-terminal...
While the aetiology of idiopathic multicentric Castleman disease (iMCD) remains unclear, involvement autoinflammatory mechanisms has been suggested. Herein we report a Japanese patient with iMCD novel heterozygous Ile729Met mutation in exon 10 Mediterranean fever (MEFV) gene.We performed genetic analysis via targeted next-generation sequencing and Sanger conducted molecular dynamics simulations to investigate hydrophobic interactions around 729th amino acid human pyrin.In February 2011,...
Dielectric properties of the hydrogen-bonded material, 5-bromo-9-hydroxyphenalenone (C(13)H(7)O(2)Br; BrHPLN), are investigated theoretically by means electronic structure calculations and Monte Carlo simulations. The density functional BrHPLN crystals have revealed that polarization per one molecule can be about 1.7 times larger than isolated monomer. It is also found there exists significant electron (0.01 e bohr(-3)) in an intermolecular C-H···O region, which, together with interatomic...
An accurate theoretical prediction of the vibrational spectrum polypeptides remains to be a challenge due (1) their conformational flexibility and (2) non-negligible anharmonic effects. The former makes search for conformers that contribute difficult, latter requires an expensive, quantum mechanical calculation both electrons vibrations. Here, we propose new approach, which implements enhanced sampling by replica-exchange molecular dynamics method, structural clustering identify distinct...
Influenza viruses are responsible for contagious respiratory illnesses in humans and cause seasonal epidemics occasional pandemics worldwide. Previously, we identified a quinolinone derivative PA-49, which inhibited the influenza virus RNA-dependent RNA polymerase (RdRp) by targeting PA–PB1 interaction. This paper reports structure optimization of resulted identification 3-((dibenzylamino)methyl)quinolinone derivatives with more potent anti-influenza activity. During optimization, hit...
Abstract To explore the potential biological activities of trifluoromethyl heterocycles, we recently developed a synthetic approach to access series α‐trifluoromethyl‐α,β‐unsaturated lactones and pyrazolinones. The compounds were tested for their antimicrobial activity, found that some had anti‐influenza viral activity. β‐aryl‐α‐trifluoromethyl α,β‐unsaturated lactone derivatives 5 g (5‐(4‐chlorophenyl)‐5‐methyl‐4‐phenyl‐3‐(trifluoromethyl)furan‐2‐one), 7 b...
Abstract Diversity of prion strains is one the most mysterious traits prions because they are mere aggregates abnormally-folded forms single protein species, (PrP Sc ), without genome. Although strain-specific properties hypothesized to be enciphered in structures PrP instead nucleotide genome, specifically what structure can code information remains an enigma due incompatibility with structural analyses. strain diversity was regarded as unique prions, recently other disease-associated...
The emergence of resistance to currently available anti-influenza drugs has heightened the need for antivirals with novel mechanisms action. influenza A virus (IAV) nucleoprotein (NP) is highly conserved and essential formation viral ribonucleoprotein (vRNP), which serves as template replication transcription. Recently, using in silico screening, we identified an antiviral compound designated NUD-1 (a 4-hydroxyquinolinone derivative) a potential inhibitor NP. In this study, further analyzed...
Synthetic routes to multi-functionalized-α-trifluoromethyl α,β-unsaturated lactones and trifluoromethyl pyrazolinones.
A similarity score of vibrational spectra is proposed to reveal the structures two conformers a pentapeptide, acetyl-SIVSF- N -methylamide. One found be 25 kJ mol −1 less stable than most one.
Abstract Intermolecular interactions in molecular crystal of 5‐bromo‐9‐hydroxyphenalenone are analyzed by means Bader's theory atoms molecules. A set criteria to ascertain the presence a hydrogen bond is applied two candidates intermolecular contacts suggested our previous work [Otaki and Ando, Phys. Chem. 2011, 13 , 10719]. It shown that they almost satisfy confirm existence CH···O bond. In addition bonding, other types interactions, such as H···H H···Br, found one candidates. The...
Prions are unconventional pathogens that encode the pathogenic information in conformations of constituent abnormal isoform prion protein (PrPSc), independently nucleotide genome. Therefore, conformational diversity PrPSc underlies existence many strains and species barriers prions, although is extremely limited. Interestingly, differences between polymorphic or species-specific residues responsible for species/strain often caused by conservative replacements hydrophobic amino acids. This...
Abstract Mechanism of strain diversity prions is a long-standing conundrum, because consist solely abnormal isoform prion protein (PrP Sc ) devoid genetic material. Pathogenic properties are determined by conformations the constituent PrP according to protein-only hypothesis, and alterations even single residue can drastically change when located at critical position for structure . Interestingly, methionine (Met) often recognized as polymorphic or species-specific residues responsible...