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NRAS DNA G-quadruplex-targeting molecules for sequence-selective enzyme inhibition 招待あり 査読あり
Yoshiki Hashimoto, Hiroki Kubo, Keiko Kawauchi and Daisuke Miyoshi
Chem. Commun. 2024年10月
担当区分：責任著者
DOI： 10.1039/D4CC03753G
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Factors Affecting Liquid-Liquid Phase Separation of RGG Peptides with DNA G-Quadruplex 招待あり 査読あり
Sumit Shil, Mitsuki Tsuruta, Keiko Kawauchi, Daisuke Miyoshi
ChemMedChem 2024年9月
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Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells. 査読あり
Keigo Araki, Takeru Torii, Kohei Takeuchi, Natsuki Kinoshita, Ryoto Urano, Rinka Nakajima, Yaxuan Zhou, Tokuo Kobayashi, Tadayoshi Hanyu, Kiyoshi Ohtani, Kimiharu Ambe, Keiko Kawauchi
Neoplasia 57 101044 2024年8月
担当区分：最終著者
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Quantitative Effects of the Loop Region on Topology, Thermodynamics, and Cation Binding of DNA G-quadruplexes 査読あり
Minori Nakata, Naoki Kosaka, Keiko Kawauchi, Daisuke Miyoshi
ACS Omega 9 35028 - 35036 2024年7月
担当区分：最終著者, 責任著者
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Development of a CaCO3 Precipitation Method Using a Peptide and Microwaves Generated by a Magnetron 査読あり
Fumihiro Kayamori, Hiroyuki Togashi, Natsumi Endo, Makoto Ozaki, Kan Hirao, Yonejiro Arimoto, Ryuji Osawa, Takaaki Tsuruoka, Takahito Imai, Kin-ya Tomizaki, Tomohiro Umetani, Nobuhiro Nakanishi, Kenji Usui
Processes 12 ( 7 ) 1327 - 1327 2024年6月
出版者・発行元：MDPI AG
Microwave applications, such as microwave ovens and mobile phones, are ubiquitous and indispensable in modern society. As the utilization of microwave technology is becoming more widespread, the effects of microwaves on living organisms and physiological processes have received increased attention. This study aimed to investigate the effects of microwaves on calcium carbonate biomineralization as a model biochemical process. A magnetron oscillator was used to generate 2450 MHz microwaves because magnetrons are relatively inexpensive and widespread. We conducted transmission electron microscopy (TEM), atomic force microscopy (AFM), TEM-electron energy-loss spectroscopy (EELS), dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC) measurements to analyze the calcium carbonate precipitates. Our findings showed the formation of string-like precipitates of calcium carbonate upon microwave irradiation from one direction, similar to those obtained using a semiconductor oscillator, as reported previously. This implied that the distribution of the frequency had little effect on the morphology. Furthermore, spherical precipitates were obtained upon microwave irradiation from two directions, indicating that the morphology could be controlled by varying the direction of microwave irradiation. Magnetrons are versatile and also used in large-scale production; thus, this method has potential in medical and industrial applications.
DOI： 10.3390/pr12071327
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Development of a CaCO3 Precipitation Method Using a Peptide and Microwaves Generated by a Magnetron 査読あり
Fumihiro Kayamori Hiroyuki Togashi Natsumi Endo Makoto Ozaki Kan Hirao Yonejiro Arimoto Ryuji Osawa Takaaki Tsuruoka Takahito Imai Kin-ya Tomizaki Tomohiro Umetani Nobuhiro Nakanishi Kenji Usui
Processes 12 ( 7 ) 1327 2024年6月
Microwave applications, such as microwave ovens and mobile phones, are ubiquitous and indispensable in modern society. As the utilization of microwave technology is becoming more widespread, the effects of microwaves on living organisms and physiological processes have received increased attention. This study aimed to investigate the effects of microwaves on calcium carbonate biomineralization as a model biochemical process. A magnetron oscillator was used to generate 2450 MHz microwaves because magnetrons are relatively inexpensive and widespread. We conducted transmission electron microscopy (TEM), atomic force microscopy (AFM), TEM-electron energy-loss spectroscopy (EELS), dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC) measurements to analyze the calcium carbonate precipitates. Our findings showed the formation of string-like precipitates of calcium carbonate upon microwave irradiation from one direction, similar to those obtained using a semiconductor oscillator, as reported previously. This implied that the distribution of the frequency had little effect on the morphology. Furthermore, spherical precipitates were obtained upon microwave irradiation from two directions, indicating that the morphology could be controlled by varying the direction of microwave irradiation. Magnetrons are versatile and also used in large-scale production; thus, this method has potential in medical and industrial applications.
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Inhibition of RNA phosphodiester backbone cleavage in the presence of organic cations of different sizes 招待あり 査読あり 国際誌
S. Yoshioka, A. Doi, and S. Nakano
ChemBioChem 25 ( 13 ) e202400276 2024年5月
共著
担当区分：最終著者, 責任著者 出版者・発行元：Wiley
Living cells contain various types of organic cations that may interact with nucleic acids. In order to understand the nucleic acid–binding properties of organic cations of different sizes, we investigated the ability of simple organic cations to inhibit the RNA phosphodiester bond cleavage promoted by Mg2+, Pb2+, and RNA-cleaving serum proteins. Kinetic analysis using chimeric DNA–RNA oligonucleotides showed that the cleavage at ribonucleotide sites was inhibited in the presence of monovalent cations comprising alkyl chains or benzene rings. The comparison of the cleavage rates in the presence of quaternary ammonium and phosphonium ions indicated that the steric hindrance effect of organic cations on their binding to the RNA backbone is significant when the cation size is larger than the phosphate–phosphate distance of a single-stranded nucleic acid. The cleavage inhibition was also observed for ribonucleotides located in long loops but not in short loops of oligonucleotide structures, indicating less efficient binding of bulky cations to structurally constrained regions. These results reveal the unique nucleic acid–binding properties of bulky cations distinct from those of metal ions.
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Hiroyuki Togawa, Takashi Okubo, Kazuki Horiuchi, Takao Yamaguchi, Elisa Tomita-Sudo, Tomoka Akita, Junji Kawakami, Satoshi Obika
Journal of Chromatography A 1721 464847 2024年4月
共著
In recent years, several small interfering RNA (siRNA) therapeutics have been approved, and most of them are phosphorothioate (PS)-modified for improving nuclease resistance. This chemical modification induces chirality in the phosphorus atom, leading to the formation of diastereomers. Recent studies have revealed that Sp and Rp configurations of PS modifications of siRNAs have different biological properties, such as nuclease resistance and RNA-induced silencing complex (RISC) loading. These results highlight the importance of determining diastereomeric distribution in quality control. Although various analytical approaches have been used to separate diastereomers (mainly single-stranded oligonucleotides), it becomes more difficult to separate all of them as the number of PS modifications increases. Despite siRNA exhibits efficacy in the double-stranded form, few reports have examined the separation of diastereomers in the double-stranded form. In this study, we investigated the applicability of non-denaturing anion-exchange chromatography (AEX) for the separation of PS-modified siRNA diastereomers. Separation of the four isomers of the two PS bonds tended to improve in the double-stranded form compared to the single-stranded form. In addition, the effects of the analytical conditions and PS-modified position on the separation were evaluated. Moreover, the elution order of the Sp and Rp configurations was confirmed, and the steric difference between them, i.e., the direction of the anionic sulfur atom, appeared to be important for the separation mechanism in non-denaturing AEX. Consequently, all 16 peak tops of the four PS modifications were detected in one sequence, and approximately 30 peak tops were detected out of 64 isomers of six PS bonds, indicating that non-denaturing AEX is a useful technique for the quality control of PS-modified siRNA therapeutics.
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細胞内環境で安定化する核酸構造を標的にした低分子薬の開発 招待あり
橋本 佳樹, 川内 敬子, 三好 大輔
MEDCHEM NEWS (日本薬学会） 34 ( 1 ) 36 - 42 2024年4月
担当区分：最終著者, 責任著者
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Basic protein- and peptide-induced stabilization of long-loop DNA G-quadruplexes 査読あり 国際誌
K. Tanabe, K. Miyazaki, H. Umeno, M. Takemoto, and S. Nakano
Biochimie 219 110 - 117 2024年4月
共著
担当区分：最終著者, 責任著者 出版者・発行元：Elsevier
The human genome contains many G-quadruplex-forming sequences, including sequences containing long single-stranded loops that are believed to be unfavorable for G-quadruplex formation. The intracellular environment of biological cells is crowded with proteins with charged surfaces. Understanding the effects of protein-rich environments is important for understanding the formation of G-quadruplexes in an intracellular environment. In this study, we investigated the structural stability of DNA G-quadruplexes in the presence of several types of globular proteins (lysozyme, cytochrome c, bovine serum albumin, myoglobin, histone proteins, and serum proteins), unstructured polypeptides (protamine and poly-l-lysine), and oligopeptides (RGG/RG-domain peptides and short repeated peptides). Thermal melting studies of G-quadruplex-forming oligonucleotides derived from the human telomeric repeat sequence revealed that environments containing high concentrations of proteins and peptides differently affected the G-quadruplex stability according to their loop lengths. We found that weak electrostatic interactions of G-quadruplex loops with basic proteins and peptides improved the stability of long-loop G-quadruplexes and the interactions were strengthened under crowded conditions simulated by dextran. The comparison of the effects of different types of proteins and peptides indicated that excluded volume interactions and structural flexibility of both DNA and polypeptide chains influenced the efficiency of their interactions. This study provides insights into long-loop G-quadruplex stability in a crowded intracellular environment and the recognition of G-quadruplexes by arginine-rich domains of G-quadruplex-binding proteins.
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Hisae Tateishi-Karimata, Keiko Kawauchi, Shuntaro Takahashi, Naoki Sugimoto
Journal of the American Chemical Society 146 ( 12 ) 8005 - 8015 2024年3月
出版者・発行元：American Chemical Society (ACS)
DOI： 10.1021/jacs.3c11160
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Yohei Takashima, Naoto Tanabe, Shintaro Tanaka, Takaaki Tsuruoka, Kensuke Akamatsu
Crystal Growth & Design 24 ( 4 ) 1766 - 1773 2024年2月
出版者・発行元：American Chemical Society (ACS)
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Cr(NO3)3 as a new etching reagent for an Al-based metal-organic framework to control its crystal size and defects 査読あり
Yohei Takashima, Naoto Tanabe, Shintaro Tanaka, Takaaki Tsuruoka, Kensuke Akamatsu
Cryst. Growth Des. 24 1766 - 1773 2024年2月
担当区分：筆頭著者, 責任著者
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Structure and thermoelectric characterization of p-Type SnTe nanobulk material synthesized by charge compensation chemical reaction 査読あり
Ryosuke Fujiwara, Yuta Ikeda, Takuto Kawaguchi, Yohei Takashima, Takaaki Tsuruoka, Kensuke Akamatsu
Energies 17 190 2024年2月
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Inhibitory Effects of Shikonin Dispersion, an Extract of Lithospermum erythrorhizon Encapsulated in β-1,3-1,6 Glucan, on Streptococcus mutans and Non-Mutans Streptococci 査読あり
Ryota Nomura, Yuto Suehiro, Fumikazu Tojo, Saaya Matayoshi, Rena Okawa, Masakazu Hamada, Shuhei Naka, Michiyo Matsumoto-Nakano, Rika Unesaki, Kazuya Koumoto, Keiko Kawauchi, Takahito Nishikata, Tatsuya Akitomo, Chieko Mitsuhata, Masatoshi Yagi, Toshiro Mizoguchi, Koki Fujikawa, Taizo Taniguchi and Kazuhiko Nakano
25 1075 2024年1月
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Inhibitory Effects of Shikonin Dispersion, an Extract of Lithospermum erythrorhizon Encapsulated in β -1,3-1,6 Glucan, on Streptococcus mutans and Non-Mutans Streptococci 査読あり
Nomura R, Suehiro Y, Tojo F, Matayoshi S, Okawa R, Hamada M, Naka S, Matsumoto-Nakano M, Unesaki R, Koumoto K, Kawauchi K, Nishikata T, Akitomo T, Mitsuhata C, Yagi M, Mizoguchi T, Fujikawa K, Taniguchi T, Nakano K
International Journal of Molecular Science 25 1075 2024年1月
共著
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Inhibitory Effects of Shikonin Dispersion, an Extract of Lithospermum erythrorhizon Encapsulated in β-1,3-1,6 Glucan, on Streptococcus mutans and Non-Mutans Streptococci. 査読あり 国際誌
Ryota Nomura, Yuto Suehiro, Fumikazu Tojo, Saaya Matayoshi, Rena Okawa, Masakazu Hamada, Shuhei Naka, Michiyo Matsumoto-Nakano, Rika Unesaki, Kazuya Koumoto, Keiko Kawauchi, Takahito Nishikata, Tatsuya Akitomo, Chieko Mitsuhata, Masatoshi Yagi, Toshiro Mizoguchi, Koki Fujikawa, Taizo Taniguchi, Kazuhiko Nakano
International journal of molecular sciences 25 ( 2 ) 2024年1月
Shikonin is extracted from the roots of Lithospermum erythrorhizon, and shikonin extracts have been shown to have inhibitory effects on several bacteria. However, shikonin extracts are difficult to formulate because of their poor water solubility. In the present study, we prepared a shikonin dispersion, which was solubilized by the inclusion of β-1,3-1,6 glucan, and analysed the inhibitory effects of this dispersion on Streptococcus mutans and non-mutans streptococci. The shikonin dispersion showed pronounced anti-S. mutans activity, and inhibited growth of and biofilm formation by this bacterium. The shikonin dispersion also showed antimicrobial and antiproliferative effects against non-mutans streptococci. In addition, a clinical trial was conducted in which 20 subjects were asked to brush their teeth for 1 week using either shikonin dispersion-containing or non-containing toothpaste, respectively. The shikonin-containing toothpaste decreased the number of S. mutans in the oral cavity, while no such effect was observed after the use of the shikonin-free toothpaste. These results suggest that shikonin dispersion has an inhibitory effect on S. mutans and non-mutans streptococci, and toothpaste containing shikonin dispersion may be effective in preventing dental caries.
DOI： 10.3390/ijms25021075
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Direct Formation of ZIF-8 Crystal Thin Films on the Surface of a Zinc Ion-Doped Polymer Substrate 査読あり
Takaaki Tsuruoka, Kaito Araki, Kouga Kawauchi, Yohei Takashima, Kensuke Akamatsu
Inorganics 12 ( 1 ) 21 - 21 2024年1月
担当区分：筆頭著者, 責任著者 出版者・発行元：MDPI AG
Thin films of metal–organic frameworks (MOFs) on polymer substrates and MOF/polymer mixed-matrix membranes play crucial roles in advancing the field of gas separation membranes. In this paper, we present a novel method for the direct formation of continuous ZIF-8 crystal films on a polymer substrate doped with Zn²+. Our approach involves ion exchange between the doped zinc ions within the substrate and sodium ions in the presence of a CH3COONa additive, as well as interfacial complexation with eluted zinc ions and 2-methylimidazole (2-MeIM). The key factors affecting the formation of ZIF-8 crystals on the substrate were the concentrations of CH3COONa and 2-MeIM. A time-course analysis revealed that the nucleation rate during the early stages of the reaction significantly affected the surface morphology of the resulting ZIF-8 crystal films. Specifically, a higher nucleation rate led to the formation of continuous small ZIF-8 crystal films. This innovative approach enables the fabrication of densely packed, uniform ZIF-8 crystal films.
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Direct formation of ZIF-8 crystal thin films on the surface of a zinc ion-doped polymer substrate 査読あり
Takaaki Tsuruoka, Kaito Araki, Kouga Kawauchi, Yohei Takashima, Kensuke Akamatsu
Inorganics 12 21 2024年1月
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“Interfacial analysis of the ion-transport process controlling the steady-state current in a two-phase electrodeposition system using polyelectrolyte membranes
S. Yamada, Y. Takashima, T. Tsuruoka, K. Akamatsu
RSC Applied Interfaces 2024年