Language：English   Publishing type：Research paper (scientific journal)  

In many repeat diseases, such as Huntington's disease (HD), ongoing repeat expansions in affected tissues contribute to disease onset, progression and severity. Inducing contractions of expanded repeats by exogenous agents is not yet possible. Traditional approaches would target proteins driving repeat mutations. Here we report a compound, naphthyridine-azaquinolone (NA), that specifically binds slipped-CAG DNA intermediates of expansion mutations, a previously unsuspected target. NA efficiently induces repeat contractions in HD patient cells as well as en masse contractions in medium spiny neurons of HD mouse striatum. Contractions are specific for the expanded allele, independently of DNA replication, require transcription across the coding CTG strand and arise by blocking repair of CAG slip-outs. NA-induced contractions depend on active expansions driven by MutSβ. NA injections in HD mouse striatum reduce mutant HTT protein aggregates, a biomarker of HD pathogenesis and severity. Repeat-structure-specific DNA ligands are a novel avenue to contract expanded repeats.

DOI： 10.1038/s41588-019-0575-8

Language：English   Publishing type：Research paper (scientific journal)  

Much recent attention has been focused on small organic molecules binding to non-canonical structures of nucleic acids, especially, RNA. The Human Genome Project and the ENCODE (encyclopedia of DNA elements) project revealed that more than 75% of the human genome is transcribed into RNA, while only ∼3% of the human genome encodes a protein. These non-protein-coding RNAs are thought to play significant roles in many cellular processes and are promising targets for drug discovery. Emerging roles of the non-coding RNAs in a variety of diseases provides enormous opportunities for pharmaceutical research on developing drugs targeting undruggable and rare diseases. During the last two decades, our laboratory has focused attention on small molecules binding to non-canonical DNA and RNA structures, especially to mismatched base pairs. Mismatch binding ligands (MBLs) we have developed are synthetic molecules designed in silico based on the hypothesis of hydrogen-bonding and semi-intercalation to DNA and RNA. Most of MBLs consists of two heterocycles having hydrogen bonding surfaces fully or partially complementary to that of nucleotide bases. In our design, each heterocycle binds to one of the mismatched bases by hydrogen bonding to form pseudo-base pairs, which would be stacked with the adjacent base pairs. The hypothesis allows us in principle to design small molecules binding to any mismatched base pairs, but it turned out not to be the case in reality. However, we have so far succeeded in developing several MBLs binding to DNA and RNA motifs of biological significance. In this review, we shall describe the hypothesis of molecular design of MBLs and its outcome regarding RNA targeting.

DOI： 10.1016/j.ymeth.2019.05.006

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Small-molecule modulators, along with antisense oligonucleotide, would be powerful tools and potential drug candidates for modulating miRNA-related gene expressions. The mechanism of the inhibitory effect of the C-bulge binding small molecule BzDANP for the Dicer processing reaction of pre-miR-136 was discussed on the data obtained by SPR, NMR, and kinetic analysis for Dicer processing. SPR and NMR analysis showed the preference of BzDANP binding to the C-bulge. Michaelis-Menten analysis suggested the formation of a ternary complex pre-miR-136-BzDANP-Dicer during the Dicer-cleavage reaction of pre-miR-136 in the presence of BzDANP. The inhibitory effect of BzDANP is likely attributed to the slower reaction from the ternary complex than that from the binary pre-miR-136-Dicer complex.

DOI： 10.1016/j.bmc.2019.03.031

Language：English   Publishing type：Research paper (scientific journal)  

Programmed -1 ribosomal frameshifting (-1PRF) is a recoding mechanism to make alternative proteins from a single mRNA transcript. -1PRF is stimulated by cis-acting signals in mRNA, a seven-nucleotide slippery sequence and a downstream secondary structure element, which is often a pseudoknot. In this study we engineered the frameshifting pseudoknot from the mouse mammary tumor virus to respond to a rationally designed small molecule naphthyridine carbamate tetramer (NCTn). We demonstrate that NCTn can stabilize the pseudoknot structure in mRNA and activate -1PRF both in vitro and in human cells. The results illustrate how NCTn-inducible -1PRF may serve as an important component of the synthetic biology toolbox for the precise control of gene expression using small synthetic molecules.

DOI： 10.1093/nar/gky689

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We here report the synthesis of novel molecule BzDANP having a three-ring benzo[c][1,8]naphthyridine system, the evaluation of its binding properties to a single nucleotide bulge in RNA duplexes, and BzDANP-induced suppression of pre-miR-29a processing by Dicer. BzDANP showed much increased affinity to the bulged RNAs as compared with the parent molecule DANP, which possesses the same hydrogen-bonding surface as BzDANP but in a two-ring [1,8]naphthyridine system. Melting temperature analysis of bulged RNAs showed that BzDANP most effectively stabilized the C-bulged RNA. Dicer-mediated processing of pre-miR-29a was suppressed by BzDANP in a concentration dependent manner. The presence of the C-bulge at the Dicer cleavage site was effective for the suppression of pre-miR-29a processing by BzDANP. These results demonstrated that the small molecule binding to the bulged site in the vicinity of the Dicer cleavage site could be a potential modulator for the maturation of pre-miRNA.

DOI： 10.1021/acschembio.6b00214

Language：English   Publishing type：Research paper (scientific journal)  

The metabolic stream of microRNA (miRNA) production, the so-called maturation process of miRNAs, became one of important metabolic paths for drug-targeting to modulate the expression of genes related to a number of diseases. We carried out discovery studies on small molecules binding to the precursor of miR-29a (pre-miR-29a) from a chemical library containing 41119 compounds (AQ library) by the fluorescent indicator displacement (FID) assay using the xanthone derivative X2SdiMe as a fluorescent indicator. The FID assay provided 1075 compounds, which showed an increase of fluorescence. These compounds were subsequently submitted to a binding analysis in a surface plasmon resonance (SPR) assay on a pre-miR-29a immobilized surface. 21 hit compounds were identified with a good reproducibility in the binding. These compounds have not been reported to bind to RNA until now and can be classified into two groups on the basis of the kinetics in the binding. To gain more information on the motif structures that could be necessary for the binding to pre-miR-29a, 19 sub-structures were selected from the hit compounds. The substructure library (SS library) which consisted of 362 compounds was prepared from the AQ library. An SPR assay of the SS library on pre-miR-29a-immobilized surface suggested that five substructures could potentially be important structural motifs to bind to pre-miR-29a. These studies demonstrate that the combination of FID-based screening of chemical library and subsequent SPR assay would be one way for obtaining practical solutions for the discovery of molecules which bind to the target pre-miRNAs.

DOI： 10.1002/chem.201502913

Language：English   Publishing type：Research paper (scientific journal)  

Determination of subcellular localization and dynamics of mRNA is increasingly important to understanding gene expression. A new convenient and versatile method is reported that permits spatiotemporal imaging of specific non-engineered RNAs in living cells. The method uses transfection of a plasmid encoding a gene-specific RNA aptamer, combined with a cell-permeable synthetic small molecule, the fluorescence of which is restored only when the RNA aptamer hybridizes with its cognitive mRNA. The method was validated by live-cell imaging of the endogenous mRNA of -actin. Application of the technology to mRNAs of a total of 84 human cytoskeletal genes allowed us to observe cellular dynamics of several endogenous mRNAs including arfaptin-2, cortactin, and cytoplasmic FMR1-interacting protein2. The RNA-imaging technology and its further optimization might permit live-cell imaging of any RNA molecules.

DOI： 10.1002/anie.201410339

Language：English   Publishing type：Research paper (scientific journal)  

A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs) and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1]) that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1) and ABCG2 (BCRP), both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.

DOI： 10.1016/j.celrep.2014.02.006

Language：English   Publishing type：Research paper (scientific journal)  

Fluorescent indicator displacement (FID) assay is a rapid and convenient assay for identifying new ligands that bind to the target molecules. In our previous studies, we have shown that a series of 2,7-diaminoalkoxy xanthone and thioxanthone derivatives can be used as fluorescent indicators for detecting the interaction between RNA and a ligand. The xanthone and thioxanthone fluorochromes showed efficient fluorescence quenching upon binding to target RNA. Subsequent displacement of the bound-fluorochrome with a ligand that binds more strongly to the target RNA led to the recovery of the fluorescence by releasing the fluorochrome from RNA. Here we report a pilot screening of a chemical library that contains 9600 structurally diverse compounds for molecules that bind to a specific miRNA precursor using the FID assay. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2013.09.007

Language：English   Publishing type：Research paper (scientific journal)  

In recent years, various biological processes have been found to be regulated by miRNA-mediated gene silencing. A small molecule that modulate the miRNA pathway will provide the biological tool for elucidating mechanisms of miRNA-mediated gene regulation, and can be the drug lead for miRNA related diseases. In this study, we demonstrated that an aminoalkoxy-substituted thioxanthone derivative interferes Dicer-mediated processing of pre-miRNA. Information about the interaction between these xanthone derivatives and pre-miRNAs will enable us to design and develop new small molecule-based inhibitors for miRNA pathway. (c) 2012 Published by Elsevier Ltd.

DOI： 10.1016/j.bmcl.2012.10.108

Language：English   Publishing type：Research paper (scientific journal)  

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 the binding of an mRNA aptamer tag to the quencher segment of the molecules. The method allows real-time detection of mRNA transcripts in vitro.

DOI： 10.1039/c1cc10393h

Language：English   Publishing type：Research paper (scientific journal)  

Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.

DOI： 10.1016/j.chembiol.2010.10.017

Language：English   Publisher：Bioorganic and Medicinal Chemistry Letters  

Base Excision Repair (BER) pathway is correlated with nucleotide repeat instability. In this report, we investigated the modulatory effects of a DNA-binding small molecule, naphthyridine azaquinolone (NA), towards BER in an in vitro system. Thermal melting analyses demonstrated binding of NA to deaminated 5’-CAG-3′/5’-CAG-3′ triads in DNA. Furthermore, binding of NA to the deaminated CAG repeat hairpin was found to partially inhibit UNG2- and APE1-catalyzed reaction, suggesting a potential mechanism for NA-induced CAG repeat contraction via BER pathway.

DOI： 10.1016/j.bmcl.2025.130152

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Bioorganic and Medicinal Chemistry  

We here report a new molecule DoNA binding to a CAG repeat RNA. DoNA is a dimer of the NA molecule that we previously reported. NA binds with high affinity to a CAG repeat DNA but not significantly to a CAG repeat RNA. Binding analyses using SPR and CSI-TOF MS indicated a significant increase in the affinity of DoNA to a single stranded CAG repeat RNA compared to NA. Systematic investigation of the RNA motifs bound by DoNA using hairpin RNA models revealed that DoNA binds to the CAG units at overhang and terminal positions, and notably, it binds to the structurally flexible internal and hairpin loop region.

DOI： 10.1016/j.bmc.2023.117580

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：eLife  

Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.

DOI： 10.7554/eLife.84338

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The stable R-loop formed during transcription induces enzyme-mediated deamination of cytosine, and the uracil in the DNA produced activates the base excision repair (BER) pathway. DNA cleavage involved in the BER pathway is thought to be one of the possible causes of trinucleotide repeat instability. Here, we performed an in vitro assay to investigate the effect of a DNA-binding small molecule, naphthyridine carbamate dimer (NCD), on BER enzyme reactions. The gel electrophoretic mobility shift assay (EMSA) and thermal melting analysis revealed the binding of NCD to a 5 '-XGG-3 '/5 '-XGG-3 ' triad (X = C or U or apurinic/ apyrimidinic site), which is a mimic of a BER enzyme substrate. Polyacrylamide gel electrophoresis (PAGE) of the reaction products of these substrates with hSMUG1 and APE1 enzymes in the presence of NCD showed that NCD interfered with the repair reaction in the 5 '-XGG-3 '/5 '-XGG-3 ' triad. These findings would broaden the potential of small molecules in modulating trinucleotide repeat instability.

DOI： 10.1021/acs.biochem.2c00344

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Circular RNA (circRNA) is a covalently closed single-stranded RNA produced from pre-mRNAs via back-splicing reaction, an alternative form of splicing. Here, we show naphthyridine carbamate dimer (NCD) upregulating the production of a circRNA from a pre-mRNA containing NCD-binding site UGGAA/UGGAA in cells, demonstrating the feasibility of small-molecule mediated circRNA production.

DOI： 10.1039/d1cc06936e

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

Selective targeting of biologically relevant RNAs with small molecules is a long-standing challenge due to the lack of clear understanding of the binding RNA motifs for small molecules. The standard SELEX procedure allows the identification of specific RNA binders (aptamers) for the target of interest. However, more effort is needed to identify and characterize the sequence-structure motifs in the aptamers important for binding to the target. Herein, we described a strategy integrating high-throughput (HT) sequencing with conventional SELEX followed by bioinformatic analysis to identify aptamers with high binding affinity and target specificity to unravel the sequence-structure motifs of pre-miRNA, which is essential for binding to the recently developed new water-soluble small-molecule CMBL3aL. To confirm the fidelity of this approach, we investigated the binding of CMBL3aL to the identified motifs by surface plasmon resonance (SPR) spectroscopy and its potential regulatory activity on dicer-mediated cleavage of the obtained aptamers and endogenous pre-miRNAs comprising the identified motif in its hairpin loop. This new approach would significantly accelerate the identification prothe compound of interest and would contribute to increase the spectrum of biomedical application.

DOI： 10.1016/j.omtn.2021.11.021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Organic Chemistry  

Small molecules targeting DNA regions with structural fluctuation are an important class of molecule as chemical probes for studying the role of these structures in biological systems and the development of neurological disorders. The molecule ANP77 we described here, where a three-atom linker connects two 2-amino-1,8-naphthyridines at the C7 position, was found to form stacked structure with protonation of naphthyridine at low pH, and bound to the internal loop consisting of C/CC and T/CC in double-stranded DNA with affinities of 4.8 and 34.4 nM, respectively. Mass spectrometry and isothermal titration calorimetry analyses determined the stoichiometry for the binding as 1:1, and chemical footprinting with permanganate and NMR structural analysis revealed that the T in the T/CC was forced to flip out toward an extrahelical position upon ANP77 binding. Protonated stacked ANP77 interacted with two adjacent cytosines through hydrogen bonding and occupied the position in the duplex by flipping out the C or T opposite CC. Finally, this study demonstrated the potential of ANP77 for binding to the sequences of biological significance with the TG(T/C)CC repeat of the PIG3 promoter and the telomere repeat CCCTAA.

DOI： 10.1021/acs.joc.1c02383

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Language：English   Publishing type：Research paper (scientific journal)  

RNA is an emerging target of next-generation drug development. Recently, new small molecules targeting RNAs were discovered by several pharmaceutical companies. Methods have been reported to identify small molecules targeting a specific RNA sequence and structural motif, however, because of diverse sequence and structural motifs potentially present in the druggable functional RNAs, large sets of structure-activity relationships (SARs) information of small molecule - RNA interactions will be required for the acceleration and efficient startup of the discovery programs toward unprecedented RNA targets. Here we describe our iterative RNA selection and compounds screening to accumulate rich information about small molecules - RNA interaction. The RNAs that selectively bind to the initial molecular target, compound 1 from our in-house chemical library (JT-library), was isolated using in vitro selection technique from a hairpin-structured RNA library mimicking precursor microRNA (pre-miRNA). Then, we engineered pre-let-7f-2 to create its mutant that can bind to compound 1 by embedding the in vitro selected RNA motif for compound 1 in the hairpin loop region. The obtained mutant pre-let-7f-2-loop-mt was used as a target for screening 316 analogs of compound 1. A surface plasmon resonance (SPR) -based screening was performed against pre-let-7f-2-loop-mt-immobilized sensor surface and we obtained four compounds that can bind to the RNA. Among these four compounds, three compounds showed higher affinity to pre-let-7f-2-loop-mt than the parental compound 1, which suggests the feasibility of our strategy for gathering the SAR information on small molecule - RNA interactions. We demonstrated only one cycle of RNA selection and compounds screening in the present study, but can continue this cycle with the selected molecule to gain new RNAs and even new RNA motifs and gather much SAR information with improved accuracy.

DOI： 10.1016/j.bmc.2021.116070

Language：English   Publishing type：Research paper (scientific journal)  

Expanded CUG repeat RNA in the dystrophia myotonia protein kinase (DMPK) gene causes myotonic dystrophy type 1 (DM1) and sequesters RNA processing proteins, such as the splicing factor muscleblind-like 1 protein (MBNL1). Sequestration of splicing factors results in the mis-splicing of some pre-mRNAs. Small molecules that rescue the mis-splicing in the DM1 cells have drawn attention as potential drugs to treat DM1. Herein we report a new molecule JM642 consisted of two 1,3-diaminoisoquinoline chromophores having an auxiliary aromatic unit at the C5 position. JM642 alternates the splicing pattern of the pre-mRNA of the Ldb3 gene in the DM1 cell model and Clcn1 and Atp2a1 genes in the DM1 mouse model. In vitro binding analysis by surface plasmon resonance (SPR) assay to the r(CUG) repeat and disruption of ribonuclear foci in the DM1 cell model suggested the binding of JM642 to the expanded r(CUG) repeat in vivo, eventually rescue the mis-splicing.

DOI： 10.1002/chem.202001572

Language：English   Publishing type：Research paper (scientific journal)  

MicroRNAs (miRNAs) are short RNAs that regulate the expression of complementary messenger RNAs and are involved in numerous human diseases. However, current detection techniques lack the sensitivity to detect miRNAs of low abundance. Moreover, at a length of 20-25 bases, miRNAs are too short for the reverse transcription (RT) polymerase chain reaction (PCR). Here we have developed a new, rapid, and simple miRNA detection system utilizing an RT primer containing a DNA tag at the 5'-end to increase the length of the cDNA. This strategy increases the length of the hybridized tagged primer and the complementary template DNA, as well as the melting temperature of the primer⋅template DNA duplex. PCR efficiency is thus increased, thereby enhancing miRNA detection sensitivity.

DOI： 10.1002/cbic.201900382

Language：English   Publishing type：Research paper (scientific journal)  

The trinucleotide repeat expansion disorders (TREDs) constitute of a group of >40 hereditary neurodegenerative human diseases associated with abnormal expansion of repeated sequences, such as CAG repeats. The pathogenic factor is a transcribed RNA or protein whose function in the cell is compromised. The disorders are progressive and incurable. Consequently, many ongoing studies are oriented at developing therapies. We have analyzed crystal structures of RNA containing CAG repeats in complex with synthetic cyclic mismatch-binding ligands (CMBLs). The models show well-defined interactions between the molecules in which the CMBLs mimic nucleobases as they form pseudo-canonical base pairs with adenosine residues and engage in extensive stacking interactions with neighboring nucleotides. The binding of ligands is associated with major structural changes of the CAG repeats, which is consistent with results of biochemical studies. The results constitute an early characterization of the first lead compounds in the search for therapy against TREDs. The crystallographic data indicate how the compounds could be further refined in future biomedical studies.

DOI： 10.1093/nar/gkz832

Language：English   Publishing type：Research paper (scientific journal)  

Expanded r(CUG) repeats are the cause of the neurological disorder myotonic dystrophy type 1 (DM1). The pathological features of DM1 include the formation of ribonuclear foci containing expanded r(CUG) repeats, which sequester the MBNL1 protein and lead to the misregulation of alternative pre-mRNA splicing. Small molecules that bind to the r(CUG) repeats and improve alternative splicing have therapeutic potential in the treatment of DM1. Herein, the synthesis of DDAP (a dimeric form of the CUG-binding molecule DAP reported previously), its binding properties to r(CUG) repeats, and its effect on the misregulation of splicing are reported. The surface plasmon resonance assay, circular dichroism spectra, and ESI-TOF mass spectrometry results confirmed the binding of DDAP to r(CUG)9 repeats. Studies on a DM1 cell model and a DM1 mouse model revealed that DDAP was partially effective in the recovery of the pre-mRNA splicing defects. The mechanism underlying this recovery was studied in vitro through a competitive binding assay, and suggested that DDAP could interfere with the binding of MBNL1 to r(CUG) repeats in a concentration-dependent manner.

DOI： 10.1002/chem.201804368

Language：English   Publishing type：Research paper (scientific journal)  

One of the important determinants in the efficiency of a molecular interaction is the necessity for conformational changes in host and/or guest molecules upon binding. In small-molecule interactions with nucleic acids, conformational changes on both molecules are often involved, especially in intercalating binding. Mismatch binding ligands (MBLs) we described here consist of two heterocycles that predominantly exist in one conformation, so it is of interest to determine if such molecules can bind to any DNA and RNA structures. One molecule, 1-NHR, which predominantly exists as the unstacked conformation in aqueous solvent, has been successfully synthesized and characterized. Compound 1-NHR did not efficiently bind to GX/Y DNA and RNA sequences, but the binding pattern is different from that of authentic MBL naphthyridine carbamate dimer. In vitro selection of RNA that specifically binds to 1-NHR was performed from pre-miR-29a loop library RNA, and one RNA, to which 1-NHR bound with high affinity, has been successfully identified. Although it was anticipated that 1-NHR, with a predominantly unstacked conformation, would show entropy-driven binding, isothermal titration calorimetry analysis suggested that the binding of 1-NHR to RNA was enthalpy driven with an apparent K-d of about 100nm.

DOI： 10.1002/asia.201701293

Language：English   Publishing type：Research paper (scientific journal)  

A naphthyridine carbamate tetramer (NCT8) is a synthetic compound, which selectively binds to nucleic acids containing CGG/CGG sequence. Although NCT8 is a promising compound for a wide range of DNA and RNA based biotechnology such as modulation of specific gene expression, little is known about its behavior in human cells. In the present study, we investigated the changes induced in gene expression by NCT8. Genes differentially expressed in the presence of NCT8 in HeLa cells were identified by whole-transcriptome analysis. The whole-transcriptome analysis showed that NCT8 significantly induced up-regulation of specific genes, whose promoter region has GC-rich sequence. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2017.06.006

Language：English   Publishing type：Research paper (scientific journal)  

The development of small molecules that can recognize specific RNA secondary and tertiary structures is currently an important research topic for developing tools to modulate gene expression and therapeutic drugs. Expanded CUG trinucleotide repeats, known as toxic RNA, capture the splicing factor MBNL1 and are causative of neurological disorder myotonic dystrophy type 1 (DM1). Herein, the rational molecular design, synthesis, and binding analysis of 2,9-diaminoalkyl-substituted 1,10-phenanthroline (DAP), which bound to CUG trinucleotide repeats, is described. The results of melting temperature (T-m) analyses, surface plasmon resonance (SPR) assay, and electrospray spray ionization time-of-flight (ESI-TOF) mass spectrometry showed that DAP bound to r(CUG)(9) but not to r(CAG)(9) and r(CGG)(9). The dual luciferase assay clearly indicated DAP bound to the r(CUG)(n) repeat by affecting the translation in vitro.

DOI： 10.1002/chem.201602741

Language：English   Publishing type：Research paper (scientific journal)  

The expansion of CAG repeats in the human genome causes the neurological disorder Huntington's disease. The small-molecule naphthyridine-azaquinolone NA we reported earlier bound to the CAG/CAG motif in the hairpin structure of the CAG repeat DNA. In order to investigate and improve NA-binding to the CAG repeat DNA and RNA, we conducted systematic structure-binding studies of NA to CAG repeats. Among the five new NA derivatives we synthesized, surface plasmon resonance (SPR) assay showed that all of the derivatives modified from amide linkages in NA to a carbamate linkage failed to bind to CAG repeat DNA and RNA. One derivative, NBzA, modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)(9) and r(CAG)(9). NBzA binding to d(CAG)(9) was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time-of-flight (ESI-TOF) mass spectrometry. For the binding to r(CAG)(9), both NA and NBzA showed stepwise binding in ESI-TOF MS, and NBzA-binding to r(CAG)(9) induced more extensive conformational change than NA-binding. The tricyclic system in NBzA did not show significant effects on the binding, selectivity, and translation, but provides a large chemical space for further modification to gain higher affinity and selectivity. These studies revealed that the linker structure in NA and NBzA was suitable for the binding to CAG DNA and RNA, and that the tricyclic benzoazaquinolone did not interfere with the binding.

DOI： 10.1002/asia.201600527

Language：English   Publishing type：Research paper (scientific journal)  

A small chemical library of 8-substituted adenine and adenosine derivatives was synthesized and examined for binding to pre-miR-29a. We found that one compound showed the affinity with 61 nM of K-d and a 10-fold stronger binding than the double-stranded RNA.

DOI： 10.1246/bcsj.20140137

Language：English   Publishing type：Research paper (scientific journal)  

The hairpin structure is one of the most common secondary structures in RNA and holds a central position in the stream of RNA folding from a non-structured RNA to structurally complex and functional ribonucleoproteins. Since the RNA secondary structure is strongly correlated to the function and can be modulated by the binding of small molecules, we have investigated the modulation of RNA folding by a ligand-assisted formation of loop-loop complexes of two RNA hairpin loops. With a ligand (NCT6), designed based on the ligand binding to the G-G mismatches in double-stranded DNA, we successfully demonstrated the formation of both inter- and intra-molecular NCT6-assisted complex of two RNA hairpin loops. NCT6 selectively bound to the two hairpin loops containing (CGG)(3) in the loop region. Native polyacrylamide gel electrophoresis analysis of two doubly-labeled RNA hairpin loops clearly showed the formation of intermolecular NCT6-assisted loop-loop complex. Forster resonance energy-transfer studies of RNA constructs containing two hairpin loops, in which each hairpin was labeled with Alexa488 and Cy3 fluorophores, showed the conformational change of the RNA constructs upon binding of NCT6. These experimental data showed that NCT6 simultaneously bound to two hairpin RNAs at the loop region, and can induce the conformational change of the RNA molecule. These data strongly support that NCT6 functions as molecular glue for two hairpin RNAs.

DOI： 10.1002/chem.201304683

Language：English   Publishing type：Research paper (scientific journal)  

Artificial riboswitches can be generated by functional coupling of an RNA aptamer for synthetic small molecule to an expression platform. RNA aptamers that can bind strongly and selectively to their target are feasible to be used for obtaining more potent artificial riboswitches. In this chapter, we describe tips and notes for in vitro selection of RNA aptamers targeting synthetic small molecules. © Springer Science+Business Media New York 2014.

DOI： 10.1007/978-1-62703-755-6_2

Language：English   Publishing type：Research paper (scientific journal)  

Here, we demonstrate that a series of naphthyridine derivatives, naphthyridine carbamate tetramer (NCTn), can bind to the RNA CGG/CGG triad comprised of two single-stranded regions of a hairpin loop and a tail. Complete suppression of the binding by a single mutation indicated simultaneous binding of NCTn between hairpin loop and single stranded tail, leading to the formation of NCTn-induced pseudoknot. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2013.04.037

Language：English   Publishing type：Research paper (scientific journal)  

A series of xanthone and thioxanthone derivatives with aminoalkoxy substituents were synthesized as fluorescent indicators for a displacement assay in the study of small-moleculeRNA interactions. The RNA-binding properties of these molecules were investigated in terms of the improved binding selectivity to the loop region in the RNA secondary structure relative to 2,7-bis(2-aminoethoxy)xanthone (X2S) by fluorimetric titration and displacement assay. An 11-mer double-stranded RNA and a hairpin RNA mimicking the stem loop IIB of Rev response element (RRE) RNA of HIV-1 mRNA were used. The X2S derivatives with longer aminoalkyl substituents showed a higher affinity to the double-stranded RNA than the parent molecule. Introduction of a methyl group on the aminoethoxy moiety of X2S effectively modulated the selectivity to the RNA secondary structure. Methyl group substitution at the C1' position suppressed the binding to the loop regions. Substitution with two methyl groups on the amino nitrogen atom resulted in reducing the affinity to the double-stranded region by a factor of 40?%. The effect of methyl substitution on the amino nitrogen atom was also observed for a thioxanthone derivative. Titration experiments, however, suggested that thioxanthone derivatives showed a more prominent tendency of multiple binding to RNA than xanthone derivatives. The selectivity index calculated from the affinity to the double-stranded and loop regions suggested that the N,N-dimethyl derivative of X2S would be suitable for the screening of small molecules binding to RRE.

DOI： 10.1002/chem.201103932

Language：Japanese   Publishing type：Research paper (other academic)  

Determination of the molecular targets of natural products has had profound impacts on studies of complex cellular machinery. Natural products are often coevolved with proteins targets and thereby likely to exhibit high selectivity to the human counterparts of those targets. Here we report isolation of a selective protein target of aurilide, a potent cytotoxic marine natural product. The ability of aurilide at low concentrations to induce apoptosis in human cancer cells has encouraged a range of biological analyses. Nonetheless, its mechanism of action has remained unknown. To identify the target of this potent cytotoxic molecule, we biochemically isolated a selective aurilide -binding protein, prohibitin 1 (PHB1). Our mechanistic analyses indicate that the interaction of aurilide with PHB1 in mitochondria activates the proteolytic processing of optic atrophy 1 (OPA1), leading to mitochondrial fragmentation and apoptosis.

DOI： 10.24496/tennenyuki.53.0_55

Language：English   Publishing type：Research paper (scientific journal)  

Although a number of genomic and biochemical technologies are now used to elucidate the mechanisms of action of bioactive small molecules, affinity-based isolation of molecular targets is a classic, but still powerful, approach. This review highlights recent cases where biochemical isolation of target proteins of bioactive small molecules highlighted general strategies for a successful isolation and identification of molecular targets. This review is intended to be both an update on the most recent findings for those already active in the field of forward chemical genetics and a guide for scientists entering this burgeoning field.

DOI： 10.1016/j.chembiol.2010.05.015

Language：English   Publishing type：Research paper (scientific journal)  

A novel analog of nucleic acids bearing an optically active serine ester backbone, serine-based nucleobase-linked polyester (SNE), was synthesized. Monomers containing a thymine base were synthesized from l- and d-serines. Furthermore, reaction conditions were thoroughly examined for the ester bond formation by using a new phosphonium-type condensing reagent on a solid support without racemization. The release of the dimer from the resin was also investigated using a new type of linker, which could be cleaved under neutral conditions. © 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2006.02.076

Language：English   Publishing type：Research paper (scientific journal)  

A novel linker cleavable under neutral conditions has been developed for the solid-phase synthesis of base-labile compounds. The linker is comprised of a 3-azidomethyl-4-hydroxybenzyl alcohol moiety, and the azidomethyl group in the linker is readily converted to an aminomethyl group by treatment with a phosphine reagent in the presence of water to result in an intramolecular cyclization to release the compounds. Using the linker, a base-labile dinucleoside methyl phosphate was synthesized on a highly cross-linked polystyrene (HCP) support and cleaved successfully from the resin without decomposition of the product. © 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2006.01.135

Event date： 2022.11

Language：English  

Venue：東京-葛飾   Country：Japan  

A rapid method for obtaining the interacting pairs of RNA-small molecule and its statistical analysis

Event date： 2022.11

Language：English  

Venue：東京-葛飾   Country：Japan  

Evaluation of the effect of small-molecule binding to mRNA on ribosomal frameshifting in SARS-CoV-2

Event date： 2022.11

Language：English   Presentation type：Oral presentation (general)  

Venue：Tokyo-Katsushika   Country：Japan  

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Event date： 2022.11

Language：English   Presentation type：Poster presentation  

Venue：Tokyo-Katsushika   Country：Japan  

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Event date： 2022.11

Language：English   Presentation type：Poster presentation  

Venue：Tokyo-Katsushika   Country：Japan  

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Event date： 2022.11

Language：English   Presentation type：Poster presentation  

Venue：Tokyo-Katsushika   Country：Japan  

researchmap

Event date： 2021.12

Language：English  

Venue：Online   Country：Other  

Comprehensive analysis of small molecule-target RNA pairs toward profiling small-molecule binders of RNA

Event date： 2021.11

Language：Japanese  

Venue：Online   Country：Other  

RNAを標的とする低分子の探索と応用

Event date： 2020.12

Language：English  

Venue：Online   Country：Other  

Comprehensive Analysis of Dicer Substrates by High-Throughput Sequencing Identified New Target RNA Motifs for Small Molecules

Event date： 2015.12

Language：Japanese  

Venue：兵庫-神戸   Country：Japan  

小分子による–1リボソーマルフレームシフト誘起とタンパク質の輸送・局在制御への応用

Event date： 2014.3

Language：Japanese  

Venue：愛知-名古屋   Country：Japan  

RNAの構造・機能を制御する小分子化合物の開発

Event date： 2011.12

Language：English  

Venue：神奈川-横浜   Country：Japan  

Fluorescent indicator displacement assay for the discovery of RNA-binding ligands

Event date： 2023.11

Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2023.11

Language：English  

Venue：宮崎   Country：Japan  

Evaluation of APOBEC-catalyzed cytosine deamination for the repeat DNAs with binding small molecules binding

Event date： 2023.11

Language：English   Presentation type：Poster presentation  

Venue：Miyazaki   Country：Japan  

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Event date： 2022.11

Language：English  

Venue：東京-葛飾   Country：Japan  

Inhibition of the Activity of Base Excision Repair Enzymes by Mismatch Binding Ligand Binding to Uracil-containing DNA

Event date： 2022.11

Language：English  

Venue：東京-葛飾   Country：Japan  

Evaluation of APOBEC-catalyzed cytosine deamination for the repeat DNAs

Event date： 2022.11

Language：English   Presentation type：Poster presentation  

Venue：Tokyo-Katsushika   Country：Japan  

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Event date： 2022.11

Language：English   Presentation type：Poster presentation  

Venue：Tokyo-Katsushika   Country：Japan  

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Event date： 2022.3

Language：English  

Venue：Online   Country：Other  

The binding motif of naphthyridine-azaquinolone dimer (NAD) in CAG-repeat RNA

Event date： 2022.3

Language：English  

Venue：Online   Country：Other  

Modulation of APOBEC-catalyzed cytosine deamination by a small molecule binding to DNA

Event date： 2022.3

Language：English  

Venue：Online  

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Event date： 2022.3

Language：English  

Venue：Online  

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Event date： 2021.12

Language：English  

Venue：Online   Country：Other  

Using machine learning to classify and extract features of small-molecule libraries targeting DNA and RNA

Event date： 2021.12

Language：English  

Venue：Online   Country：Other  

Exploration and Identification for Small-molecules RNA binding motif by Dicer cleavage reaction and high throughput sequencing

Event date： 2021.12

Language：English  

Venue：Online   Country：Other  

Regulation of circular RNA biogenesis using nucleic acid binding small molecule in cellular environment

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

qPCR-based Screening Methods for Small Molecules that Modulate Dicer-mediated pre-miR-182/31/30d Processing

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

An RNA internal loop of C, U and A/CC motifs specific fluorescence probe ANP77

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Cell-based screening of chemical libraries for small molecules that target SARS-CoV-2 frameshifting signal

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Computer-aided classification of small molecules targeting CAG-repeat DNA

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Development of Exploration Method and Informatics analysis for small molecule-RNA pairs.

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Effect of Guanine-guanine Mismatch Binding Ligand on Repair Enzymes' reactions in vitro

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Identification of small molecules that can bind to the SARS-CoV-2 frameshifting signal by SPR-based screening of chemical libraries

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Modulation of cytosine deamination catalyzed by Deoxycytidine Deaminase APOBEC by binding of small molecule to DNA

Event date： 2021.11

Language：English  

Venue：Online   Country：Other  

Regulation of circular RNA biogenesis via nucleic acid binding small molecule in cells

Event date： 2021.8

Language：English  

Venue：Online   Country：Other  

Regulation of circRNA expression in cell via RNA binding small molecule

Event date： 2021.8

Language：English  

Venue：Online   Country：Other  

Machine learning-based classification in small molecules targeting CAG-repeat DNA

Event date： 2021.6

Language：English  

Venue：Online   Country：Other  

Screening of small molecules that interfere dicer-mediated processing of pre-miR-182/31/30d

Event date： 2021.3

Language：English  

Venue：Online   Country：Other  

Synthesis and the properties of naphthyridine-azaquinolone dimer (NAD) tatgeting CAG-repeat RNA

Event date： 2021.3

Language：Japanese  

Venue：Online   Country：Other  

Cell-basedスクリーニングによる SARS-CoV-2のフレームシフトシグナルを標的とする小分子の探索

Event date： 2021.3

Language：Japanese  

Venue：Online   Country：Other  

Dicer切断産物のハイスループットシーケンシングによる RNA-小分子結合モチーフの同定

Event date： 2021.3

Language：English  

Venue：Online   Country：Other  

Regulation of circular RNA biogenesis via RNA binding small molecule

Event date： 2021.3

Language：Japanese  

Venue：Online   Country：Other  

SARS-CoV-2フレームシフトシグナルを標的とする低分子化合物の表面プラズモン共鳴(SPR)アッセイによるスクリーニング

Event date： 2020.3

Language：English  

Venue：千葉-野田   Country：Japan  

Synthesis and the properties of NA Dimer

Event date： 2020.3

Language：Japanese  

Venue：千葉-野田   Country：Japan  

Dicer切断反応を指標としたRNA結合分子標的配列の網羅的解析

Event date： 2020.1

Language：English  

Venue：兵庫-淡路島   Country：Japan  

Controlling -1 ribosomal frameshifting by small molecules in cells

Event date： 2019.7

Language：English  

Venue：兵庫-神戸   Country：Japan  

Kinetic analysis of the inhibitory effect of BzDANP on Dicer cleavage of pre-miR-136

Event date： 2019.6

Language：English  

Venue：Krakow   Country：Poland  

Structural insights into synthetic ligands targeting A-A pairs in disease-related CAG RNA repeats

Event date： 2019.6

Language：English  

Venue：Krakow   Country：Poland  

Exploration of RNA sequences in pre-miRNA affecting the efficiency of Dicer cleavage reactions by the small molecules binding

Event date： 2019.3

Language：Japanese  

Venue：兵庫-岡本   Country：Japan  

Dicer切断を阻害するRNA結合分子標的配列の網羅的解析

Event date： 2018.11

Language：English  

Venue：京都   Country：Japan  

Synthetic small molecule-stabilized RNA pseudoknot as an activator for –1 ribosomal frameshifting

Event date： 2018.11

Language：English  

Venue：京都   Country：Japan  

Development of Isoquinoline Ligand Binding to r(CUG) Repeats

Event date： 2018.8

Language：English  

Venue：Calfornia   Country：United States  

Development of Isoquinoline Ligand Binding to r(CUG) Repeats

Event date： 2018.6

Language：Japanese  

Venue：東京   Country：Japan  

Rational design of CUG repeat binging molecule targeting Myotonic Dystrophy type 1

Event date： 2017.11

Language：English  

Venue：東京   Country：Japan  

Novel isoquinoline derivatives that inhibit MBNL1-CUG repeat interaction in Myotonic Dystrophy type1

Event date： 2017.6

Language：Japanese  

Venue：北海道-札幌   Country：Japan  

A Novel Riboswitch Strategy by Utilize Mismatch Binding Ligand (MBL)

Event date： 2017.5 - 2017.6

Language：English  

Venue：Prague   Country：Czech Republic  

Designing small molecules targeting CUG repeats causing Myotonic Dystrophy type 1

Event date： 2016.9

Language：English  

Venue：熊本-熊本   Country：Japan  

In vitro selection of pre-miR-29a loop mutant against the cyclic mismatch binding ligand (CMBL)

Event date： 2016.6

Language：Japanese  

Venue：京都   Country：Japan  

小分子化合物によるマイクロRNA生成阻害の速度論的解析

Event date： 2016.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

CAGリピートDNAおよびRNAを標的とした ナフチリジンーアザキノロン誘導体の開発と 転写および翻訳への阻害効果

Event date： 2016.3

Language：Japanese  

Venue：京都   Country：Japan  

Ligand-inducible –1 ribosomal frameshifting in the cells

Event date： 2015.12

Language：English  

Venue：Hawaii   Country：United States  

SPR-based in vitro selection of pre-miRNA loop mutant molecules that bind to the restrained naphthyridine dimer

Event date： 2015.12

Language：English  

Venue：Hawaii   Country：United States  

A small-molecule inhibitor of pre-miR-29 maturation

Event date： 2015.12

Language：English  

Venue：Hawaii   Country：United States  

Analysis of binding of naphthyridine-azaquinolone derivatives to CAG repeats RNA

Event date： 2015.11 - 2015.12

Language：Japanese  

Venue：京都   Country：Japan  

CAGリピートRNAを標的としたナフチリジン-アザキノロン誘導体の機能評価

Event date： 2015.11

Language：Japanese  

Venue：大阪-吹田   Country：Japan  

小分子誘起型–1リボソームフレームシフトによる遺伝子発現制御システムの開発

Event date： 2015.10

Language：English  

Venue：Berlin   Country：Germany  

Regulation of gene expression by ligand-inducible –1 ribosomal frameshifting

Event date： 2015.9

Language：English  

Venue：兵庫-姫路   Country：Japan  

Synthesis and Binding Property of Naphthyridine-Azaquinolone Derivatives Targeting (CAG)n Repeat RNA

Event date： 2015.9

Language：English  

Venue：兵庫-姫路   Country：Japan  

Small molecule-Loop Interaction that interferes the maturation on process of pre-miRNA by Dicer

Event date： 2015.7

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

CAGリピートDNAおよびRNAとナフチリジンーアザキノロン誘導体とのSPRによる結合評価

Event date： 2015.6

Language：Japanese  

Venue：宮城-仙台   Country：Japan  

マイクロRNA前駆体結合分子の探索

Event date： 2015.5

Language：English  

Venue：Wisconsin   Country：United States  

Regulation of gene expression by ligand-inducible –1 ribosomal frameshifting

Event date： 2015.5

Language：English  

Venue：Wisconsin   Country：United States  

In vitro selection of pre-miRNA loop mutant molecules that bind to the restrained naphthyridine dimer

Event date： 2015.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

小分子で制御するリボソームフレームシフトを用いた遺伝子発現制御

Event date： 2015.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

BzDANPによるRNAプロセシング阻害の速度論的解析

Event date： 2015.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

RNA結合性小分子の創成を指向したエンタルピー駆動型分子の設計と合成

Event date： 2015.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

SPRを用いたin vitro selectionによるRND(the restrained naphthyridine dimer)結合性RNAアプタマーの探索

Event date： 2015.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

Synthesis of circular mismatch binding ligands and their binding properties to DNA and RNA

Event date： 2015.3

Language：Japanese  

Venue：兵庫-神戸   Country：Japan  

小分子とトリヌクレオチドリピートDNAおよびRNAとのSPRによる結合評価

Event date： 2014.11

Language：English  

Venue：福岡-北九州   Country：Japan  

Suppression of miR-29a maturation by synthetic ligand

Event date： 2014.11

Language：English  

Venue：福岡-北九州   Country：Japan  

In vitro selection of pre-miR-29a loop mutant library against the restrained naphthyridine dimer

Event date： 2014.8

Language：English  

Venue：Poznan   Country：Poland  

Regulation of –1ribosomal frameshifting by ligand-induced RNA pseudoknot formation

Event date： 2014.6

Language：Japanese  

Venue：大阪-豊中   Country：Japan  

小分子によるリボソームフレームシフトの制御

Event date： 2014.6

Language：Japanese  

Venue：大阪-豊中   Country：Japan  

8位アリール置換型アデニン誘導体の合成とpre-miR-29aに対する結合評価

Event date： 2014.6

Language：Japanese  

Venue：大阪-豊中   Country：Japan  

小分子によるmiR-29a成熟過程の阻害

Event date： 2014.6

Language：English  

Venue：Quebec   Country：Canada  

Synthesis and Evaluation of 8-substituted Adenine Derivatives as RNA Binding Molecules

Event date： 2014.3

Language：Japanese  

Venue：愛知-名古屋   Country：Japan  

配座を制限したナフチリジン誘導体の合成と核酸への結合評価

Event date： 2014.3

Language：Japanese  

Venue：愛知-名古屋   Country：Japan  

小分子によるRNAシュードノット構造の形成とフレームシフトの制御への応用

Event date： 2014.3

Language：Japanese  

Venue：愛知-名古屋   Country：Japan  

小分子によるマイクロRNA前駆体のプロセシング阻害

Event date： 2014.3

Language：Japanese  

Venue：愛知-名古屋   Country：Japan  

核酸に結合する小分子のエンタルピー駆動型分子設計と合成

Event date： 2014.1

Language：English  

Venue：大阪-吹田   Country：Japan  

Regulation of Ribosomal Frameshifting by Ligand-inducible Formation of RNA Pseudoknot

Event date： 2013.12

Language：English  

Venue：大阪-吹田   Country：Japan  

Synthesis of RNA bulge binding small molecule and application to inhibitor of Dicer cleavage reaction

Event date： 2013.12

Language：English  

Venue：大阪-吹田   Country：Japan  

Development of potential small-molecule inhibitors of pre-miRNA processing

Event date： 2013.11

Language：English  

Venue：神奈川-横浜   Country：Japan  

Synthesis of the restrained naphthyridine dimer and the exploration for binding RNA by in vitro selection

Event date： 2013.10

Language：English  

Venue：Taipei   Country：Taiwan, Province of China  

Inhibition of hairpin RNA processing by Dicer using RNA-binding small molecules

Event date： 2013.6

Language：Japanese  

Venue：東京   Country：Japan  

小分子で誘起されたRNAシュードノット構造によるフレームシフト機構の制御

Event date： 2013.6

Language：English  

Venue：Davos   Country：Switzerland  

Translational regulation by ligand-inducible formation of RNA pseudoknot

Event date： 2013.6

Language：English  

Venue：Davos   Country：Switzerland  

Suppression of miR-29a maturation by ligand binding

Event date： 2013.6

Language：English  

Venue：Davos   Country：Switzerland  

Targeting secondary structures of pre-miRNA by small molecules : Development of potential inhibitors of pre-miRNA processing

Event date： 2013.3

Language：Japanese  

Venue：滋賀-草津   Country：Japan  

RNA結合性化合物を用いたマイクロRNA前駆体プロセシングの調節

Event date： 2013.3

Language：Japanese  

Venue：滋賀-草津   Country：Japan  

G-Gミスマッチ結合性リガンドで誘起されるシュードノット構造を用いた遺伝発現制御システムの開発

Event date： 2013.3

Language：Japanese  

Venue：滋賀-草津   Country：Japan  

RNAに結合する小分子のエンタルピー駆動型分子設計と合成

Event date： 2013.3

Language：Japanese  

Venue：滋賀-草津   Country：Japan  

RNAに結合する小分子のエントロピー駆動型分子設計と合成

Event date： 2013.3

Language：Japanese  

Venue：滋賀-草津   Country：Japan  

RNAバルジ結合性小分子の合成とDicer切断反応の阻害剤としての利用

Event date： 2012.11

Language：English  

Venue：愛知-名古屋   Country：Japan  

Translation regulation of gene expression by small molecule-induced pseudoknot formation

Event date： 2012.11

Language：English  

Venue：京都   Country：Japan  

Synthesis of Small Molecule Library for pre-miRNA Secondary Structures

Event date： 2012.5 - 2012.6

Language：English  

Venue：Ann Arbor-Michigan   Country：United States  

Synthesis of Small Molecule Library for pre-miRNA Secondary Structures

Event date： 2012.5 - 2012.6

Language：English  

Venue：Ann Arbor-Michigan   Country：United States  

High-throughput Screening of Chemical Libraries for the Discovery of RNA-binding Compounds

Event date： 2012.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

大規模化合物ライブラリーのスクリーニングによる，RNA結合性化合物の探索

Event date： 2012.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

RNAを標的とする創薬を指向した小分子ライブラリーの合成

Event date： 2011.11

Language：English  

Venue：北海道-札幌   Country：Japan  

Evaluation of Xanthone and Thioxanthone Derivatives as Fluorescent Displacement Assay Indicator Based on Their Structure-Binding Studies to RNA

Event date： 2011.9

Language：Japanese  

Venue：茨城-つくば   Country：Japan  

キサントン誘導体のRNA 小分子間相互作用を検出するディスプレイスメントアッセイ指示薬としての評価

Event date： 2011.6

Language：English  

Venue：京都   Country：Japan  

Development of a method for detecting small molecule-miRNA interactions

Event date： 2011.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

マイクロＲＮＡ-低分子化合物の相互作用を検出するアッセイ法の開発

Event date： 2011.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

RNAを標的とする小分子ライブラリーの合成

Event date： 2010.1

Language：English  

Venue：韓国-釜山   Country：Japan  

Small molecule-based FRET probes for specific RNA targets

Event date： 2006.3

Language：Japanese  

Venue：千葉-船橋   Country：Japan  

中性条件下切り出し可能なリンカーを用いたセリン骨格を有する新規核酸類縁ポリエステルの固相合成

Event date： 2005.10

Language：Japanese  

Venue：大阪-豊中   Country：Japan  

中性条件下切り出し可能なリンカーを用いたセリン骨格を有する新規核酸類縁ポリエステルの固相合成

Event date： 2005.3

Language：Japanese  

Venue：神奈川-横浜   Country：Japan  

中性条件下切り出し可能なリンカーを用いたセリン骨格を有する新規核酸類縁ポリエステルの固相合成

Event date： 2003.10

Language：Japanese  

Venue：千葉-木更津   Country：Japan  

セリン骨格を有する新規核酸類縁ポリエステルの固相合成

Event date： 2003.3

Language：Japanese  

Venue：東京-西早稲田   Country：Japan  

セリン骨格を有する新規核酸類縁ポリエステルの固相合成

Language：English  

Language：Others  

Identification of the Cardiac Beta-Adrenergic Receptor Protein: Solubilization and Purification by Affinity Chromatography

Language：Others