A5062846622- Click Chemistry and Applications
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Chemical Synthesis and Analysis
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
- Microbial Natural Products and Biosynthesis
- Epigenetics and DNA Methylation
- Cyclization and Aryne Chemistry
- Vitamin D Research Studies
- Estrogen and related hormone effects
- DNA and Nucleic Acid Chemistry
- Peptidase Inhibition and Analysis
- Cancer, Lipids, and Metabolism
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Peroxisome Proliferator-Activated Receptors
- 3D Printing in Biomedical Research
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Bioactive Compounds and Antitumor Agents
Kyoto Bunkyo University
2016-2025
Kyoto University
2016-2025
Fudan University
2019-2025
Kyoto University Institute for Chemical Research
2014-2024
Fukuoka Institute of Technology
2024
Material Sciences (United States)
2009-2023
Instituto de Investigaciones Químicas
1994-2023
Japan Agency for Medical Research and Development
2017-2021
RIKEN Center for Sustainable Resource Science
2019
Kyoto College of Medical Science
2018
Human pluripotent stem cells (hPSCs), including embryonic and induced cells, are potentially useful in regenerative therapies for heart disease. For medical applications, clinical-grade cardiac must be produced from hPSCs a defined, cost-effective manner. Cell-based screening led to the discovery of KY02111, small molecule that promotes differentiation cardiomyocytes. Although direct target KY02111 remains unknown, results present study suggest by inhibiting WNT signaling but manner is...
Activation domains are functional modules that enable sequence-specific DNA binding proteins to stimulate transcription. The structural basis for the function of activation is poorly understood. A combination nuclear magnetic resonance (NMR) and biochemical experiments revealed minimal acidic domain herpes simplex virus VP16 protein undergoes an induced transition from random coil α helix upon its target protein, hTAF II 31 (a human TFIID TATA box – protein-associated factor). Identification...
The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an embryonic germ layer that gives rise kidneys. In order achieve this goal, establishing efficient, stable and low-cost method for differentiating IM small molecules is required. study, we identified two retinoids, AM580 TTNPB, as potent inducers by high-throughput chemical screening, established rapid (five days) efficient...
Tumor cell plasticity contributes to functional and morphologic heterogeneity. To uncover the underlying mechanisms of this plasticity, we examined glioma stem-like cells (GSC) where found that biologic interconversion between GSCs differentiated non-GSCs is functionally plastic accompanied by gain or loss polycomb repressive complex 2 (PRC2), a modifies chromatin structure. PRC2 mediates lysine 27 trimethylation on histone H3 in GSC it affected pluripotency development-associated genes...
Enhanced de novo lipogenesis mediated by sterol regulatory element-binding proteins (SREBPs) is thought to be involved in nonalcoholic steatohepatitis (NASH) pathogenesis. In this study, we assessed the impact of SREBP inhibition on NASH and liver cancer development murine models. Unexpectedly, via deletion cleavage-activating protein (SCAP) exacerbated injury, fibrosis, carcinogenesis despite markedly reduced hepatic steatosis. These phenotypes were ameliorated restoring function....
Despite the unprecedented therapeutic potential of immune checkpoint antibody therapies, their efficacy is limited partly by dysfunction T cells within cancer microenvironment. Combination therapies with small molecules have also been explored, but clinical implementation has met significant challenges. To search for antitumor immunity activators, present study developed a cell-based system that emulates cancer-attenuated cells. The screening 232 natural products containing electrophilic...
Identification of protein targets bioactive small molecules has been a technical hurdle chemical genetics. Here we report polyproline-rod approach to isolating from cell lysates. The results indicate that insertion long, rigid polyproline helix between small-molecule bait and biotin tag boosts the capacity affinity purification thereby permits isolation low-abundance or low-affinity proteins. In course proof-of-concept experiments, isolated glyoxalase 1 (GLO1) as new target indomethacin,...
Abstract Tyrosine nitration of proteins is one the most important oxidative post‐translational modifications in vivo. A major obstacle for its biochemical and physiological studies lack efficient chemoselective protein tyrosine reagents. Herein, we report a generalizable strategy light‐controlled by employing biocompatible dinitroimidazole Upon 390 nm irradiation, dinitroimidazoles efficiently convert residues into 3‐nitrotyrosine peptides with fast kinetics high chemoselectivity under...
The structural diversity of chemical libraries, which are systematic collections compounds that have potential to bind biomolecules, can be represented by latent space. A space is a projection compound structure into mathematical based on several molecular features, and it express within library in order explore broader generate novel structures for drug candidates. In this study, we developed deep-learning method, called NP-VAE (Natural Product-oriented Variational Autoencoder), variational...
Transcriptional activation domains share little sequence homology and generally lack folded structures in the absence of their targets, aspects that have rendered difficult to characterize. Here, a combination biochemical nuclear magnetic resonance experiments demonstrates domain tumor suppressor p53 has an FXXΦΦ motif (F, Phe; X, any amino acids; Φ, hydrophobic residues) folds into α-helix upon binding one its hTAF II 31 (a human TFIID TATA box-binding protein-associated factor). MDM2,...
The candidate tumor suppressor ING1was identified in a genetic screen aimed at isolation of human genes whose expression is suppressed cancer cells. It may function as negative growth regulator the p53 signal transduction pathway. However, its molecular mechanism not clear. ING1locus encodes alternative transcripts p47ING1a, p33ING1b, and p24ING1c. Here we report differential association protein products ING1 with mSin3 transcriptional corepressor complex. p33ING1b associates Sin3, SAP30,...
Abstract Determination of subcellular localization and dynamics mRNA is increasingly important to understanding gene expression. A new convenient versatile method reported that permits spatiotemporal imaging specific non‐engineered RNAs in living cells. The uses transfection a plasmid encoding gene‐specific RNA aptamer, combined with cell‐permeable synthetic small molecule, the fluorescence which restored only when aptamer hybridizes its cognitive mRNA. was validated by live‐cell endogenous...
TRPA1 is a member of the transient receptor potential (TRP) cation channel family that expressed primarily on sensory neurons. This chemosensor activated through covalent modification multiple cysteine residues with wide range reactive compounds including allyl isothiocyanate (AITC), spicy component wasabi. The present study reports potent and selective agonists TRPA1, discovered screening 1657 electrophilic molecules. In an effort to validate mode action hit molecules, we noted new...
Aplyronine A (ApA) is a marine natural product that shows potent antitumor activity. While both ApA and ApC, derivative of lacks trimethylserine ester moiety, inhibit actin polymerization in vitro to the same extent, only cytotoxicity. Therefore, molecular targets mechanisms action cells have remained unclear. We report inhibits tubulin hitherto unprecedented way. forms 1:1:1 heterotrimeric complex with tubulin, association synergistically binding polymerization. Tubulin-targeting agents...
Visible light, particularly in the blue region of spectrum, can cause cell dysfunction through generation singlet oxygen, contributing to cellular aging and age-related pathologies. Although photooxidation nucleic acids, lipids, amino acids has been extensively studied, magnitude span blue-light-induced protein damages within proteome remain largely unknown. Herein we present a chemoproteomic approach mapping blue-light-damaged proteins live mammalian cells by exploiting nucleophilic alkyne...
NFATc (a member of the family nuclear factors activated T cells) is a transcriptional factor responsible for Ca 2+ -inducible activation cytokine genes during immune response. In resting cells, retained in cytoplasm by mechanism that depends on multiple phosphorylations an N-terminal regulatory domain. Physical interaction with and dephosphorylation -activated calcineurin (Cn) allows protein to enter nucleus, where it binds specific sites gene promoters. Previous studies had identified...
Regulation of gene expression by transcription factors touches many aspects eukaryotic biology, and its systematic, external control organic molecules represents a challenge in chemistry. Here we report the design completely organic, nonpeptidic compound that mimics factor. The takes advantage specific DNA-binding affinity hairpin polyamide molecule ability wrenchnolol to bind Sur-2 subunit human mediator complex. hybrid these two activates reporter vitro promoter-dependent manner through...
Cell-based image screening of 12 000 small molecules with aromatic groups was carried out, and 31 were identified as having potential fluorescent probes for living cells. One candidate is the first probe that specifically stains mitochondrial surfaces. Spectroscopic analyses indicate molecule undergoes bioconversion to be within Detailed facts importance specialist readers are published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made...
A method was developed that uses small molecules as fluorescent probes to detect specific mRNAs. In this approach, the fluorescence of fluorophore–quencher conjugates is restored by binding an mRNA aptamer tag quencher segment molecules. The allows real-time detection transcripts in vitro.