A5026832980- Microbial Natural Products and Biosynthesis
- Studies on Chitinases and Chitosanases
- Carbohydrate Chemistry and Synthesis
- Enzyme Production and Characterization
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- Plant biochemistry and biosynthesis
- HIV/AIDS drug development and treatment
- Fungal Biology and Applications
- Oxidative Organic Chemistry Reactions
- HIV Research and Treatment
- Biochemical and Structural Characterization
- Chemical synthesis and alkaloids
- Marine Sponges and Natural Products
- Natural product bioactivities and synthesis
- Alkaloids: synthesis and pharmacology
- Traditional and Medicinal Uses of Annonaceae
- Immune cells in cancer
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Bioactive Compounds and Antitumor Agents
- Cancer therapeutics and mechanisms
Kitasato University
2012-2025
Kitasato Institute Hospital
2003-2025
Tohoku University
2012-2025
University of Pennsylvania
2010-2019
Japan Radioisotope Association
2012
Kyorin University
2002
Hirosaki University
1975
Nonenzymatic reactions sometimes construct complex structures observed in natural products, showing us unique chemical reactions. In our exploration of we identified a novel type isochromene-derived polyketide dimer 7 with 6/6/6/6/6 five-ring system from Chaetomium indicum along several new related polyketides. We demonstrated that isochromene 6 and its oxidized derivative 8 undergo nonenzymatic dimerization under acidic conditions to give 7. Furthermore, density functional theory (DFT)...
LaeA is a putative nuclear methyltransferase protein that epigenetically influences secondary metabolite production in fungi. has drawn attention as one of the promising approaches to activate fungal chemical production, and laeA gene been introduced into some strains with aim producing metabolic changes mainly based on evaluation mycotoxicity. However, these studies were applied for limited species, its utility versatility broad species remained unclear. In this study, 47 selected composed...
Abstract The discovery of novel natural products (NPs) from diverse microorganisms is essential for advancing drug discovery. In this study, a chemical investigation approach was employed NP exploration using the genus Paraconiothyrium sp. isolated root soil Ficus microcarpa on Noho Island, Okinawa. Consequently, we five compounds, including new chromone, nohocumone ( 1 ), as well four known chromone 2 10‐norparvulenone 3 sclerotinin A 4 and calbistrin 5 culture broth FKR‐0637. planar...
Efforts to develop therapeutic agents that inhibit HIV-1 entry have led the identification of several small molecule leads. One most promising is NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, central oxalamide linker, tetramethylpiperidine moiety. In this study, we characterized structurally interactions four analogues containing meta-fluoro substitution on ring various heterocyclic replacements group. The addition...
Pancreatic cancer is one of the most difficult types to treat because its high mortality rate due chemotherapy resistance. We previously reported that combined treatment with gefitinib (GEF) and clarithromycin (CAM) results in enhanced cytotoxicity GEF along endoplasmic reticulum (ER) stress loading non-small cell lung lines. An epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as induces autophagy a pro-survival role, whereas CAM inhibits flux various Pronounced...
By mining fungal genomic information, a noncanonical iterative type I PKS fused with an N-terminal adenylation-thiolation didomain, which catalyzes the formation of naringenin chalcone, was found. Structural prediction and molecular docking analysis indicated that C-terminal thioesterase domain involved in Claisen-type cyclization. An enzyme responsible for (2S)-flavanone biosynthesis flavonoids also identified. Collectively, these findings demonstrate unprecedented biosynthetic machinery...
A first asymmetric total synthesis and determination of the absolute configuration neoxaline has been accomplished through highly stereoselective introduction a reverse prenyl group to create quaternary carbon stereocenter using (-)-3a-hydroxyfuroindoline as building block, construction indoline spiroaminal via cautious stepwise oxidations with cyclizations from indoline, assembly (Z)-dehydrohistidine, photoisomerization unnatural (Z)-neoxaline natural (E)-neoxaline key steps.
HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive for inhibition. Entry inhibitors with broad-range activity against diverse isolates of may be extremely useful as lead compounds development therapies or prophylactic microbicides. To facilitate identification such inhibitors, we have constructed cell-cell fusion system capable simultaneously monitoring inhibition efficiency specificity. In...
ABSTRACTThis study investigated the effects of presence a familiar pet dog on brain activity and psychophysiology in human volunteers. Fourteen participants (2 men, 12 women; mean age ± SD = 43.0 10.8 years) were enrolled study. Uptake 18F-2-fluoro-2-deoxyglucose ([18F]FDG) whole-brain positron emission tomography (PET) scans (but without interaction) absence their own was analyzed. In addition, an electrocardiograph recorded to assess heart rate variability. Psychological condition...
Significance Several in situ click chemistry studies have been reported. To date, there is evidence to indicate that proteins act as mold between azide and alkyne fragments by X-ray analysis of protein–ligand complexes. However, only “postclick” structural has available. We succeeded obtaining crystal structures a chitinase complexed with an inhibitor O -allyl oxime fragment mimic partner, revealing mechanism for accelerating triazole formation chitinase. This example express the “preclick”...
Abstract The total synthesis of the indole alkaloids, neoxaline, oxaline and meleagrin A, all containing a unique indoline spiroaminal framework, was accomplished through stereoselective introduction reverse prenyl group to congested benzylic carbon furoindoline, two‐pot transformation (containing three nitrogen atoms at appropriate positions) featured elimination carbonate assisted by adjacent imidazole moiety construct ( E )‐dehydrohistidine. absolute stereochemistry neoxaline elucidated...
Background. Streptococcus pneumoniae (pneumococcus) colonizes mucosal surfaces of the upper respiratory tract (URT), resulting in invasive disease. Macrolides are known for their immunomodulatory effects. We investigated potency macrolides to reduce pneumococcal colonization by activating host innate immunity. Methods. The kinetics colonization, cellular response, and inflammatory cytokine levels URT were assessed after nasal inoculation pneumococci. EM900 (a novel 12-membered nonantibiotic...
Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as drug development candidate, we devised mechanism to create the structural component of bestows chitinase inhibition and introduce into 14-membered macrolide scaffold. Here describe (1) designed macrolide, which exhibits ∼200-fold more potent than argifin, (2) binding modes with Serratia marcescens B, (3) computed analysis explaining reason for derivatives displaying increased...
<i>Background/Aims:</i> Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth drug-resistant bacteria; therefore, development with no antibacterial action desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin (EM900), does not possess action. <i>Methods:</i> To determine whether EM900 induced a clinically...