Article
Biochemistry & Molecular Biology
Daigo Funakoshi, Daisuke Obinata, Kyoko Fujiwara, Shinichiro Yamamoto, Kenichi Takayama, Makoto Hara, Satoru Takahashi, Satoshi Inoue
Summary: The study demonstrates that the pyrrole-imidazole polyamide modified with a DNA alkylating agent, chlorambucil (OCT1-PIP-ChB), has a significant inhibitory effect on prostate cancer cell proliferation and castration-resistant tumor growth, suggesting its potential as a therapeutic agent.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Jihang Yao, Keizo Takenaga, Nobuko Koshikawa, Yuki Kida, Jason Lin, Takayoshi Watanabe, Yoshiaki Maru, Yoshitaka Hippo, Seigi Yamamoto, Yuyan Zhu, Hiroki Nagase
Summary: A study found that a compound CCC-h1005 based on triphenylphosphonium has specific cytotoxic effects on cervical cancer cells and cisplatin-resistant cells, and can inhibit tumor growth in a HeLa tumor model without severe adverse effects. This provides a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Chemistry, Multidisciplinary
Yuki Hirose, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: The study demonstrated that the conjugation of chlorambucil to cyclic PIPs showed higher DNA alkylation activity and cytotoxicity against prostate cancer cells compared to hairpin PIP-chlorambucil conjugates. The results suggest that the novel cPIP-Chbs could be promising DNA alkylating anticancer drugs.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Xue Li, Zhaofang Shi, Tiezheng Jia
Summary: By characterizing the acid dissociation constants of four polyamides, the pharmacological properties of an anticancer polyamide can be optimized. The acidities of the polyamides tested were similar, while the pK(a) of the N-methylimidazole moieties varied with the peptide sequence and molecular architecture.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Medicine, Research & Experimental
Susumu Ikenoshita, Kazuya Matsuo, Yasushi Yabuki, Kosuke Kawakubo, Sefan Asamitsu, Karin Hori, Shingo Usuki, Yuki Hirose, Toshikazu Bando, Kimi Araki, Mitsuharu Ueda, Hiroshi Sugiyama, Norifumi Shioda
Summary: A compound called CWG-cPIP has been found to suppress the pathogenesis of both coding and noncoding CWG repeat diseases by selectively inhibiting pathogenic mRNA transcripts and reducing the accumulation of abnormal RNA and protein levels. This compound has shown promising results in mouse models, ameliorating behavioral deficits without any toxic effects.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Chemistry, Medicinal
Ming Wang, Xudong Ma, Kang Zhou, Huijuan Mao, Jiachun Liu, Xuqiong Xiong, Xiaoyin Zhao, Suresh Narva, Yoshimasa Tanaka, Yanling Wu, Chuanxin Guo, Hiroshi Sugiyama, Wen Zhang
Summary: A small-molecule Py-Im polyamide was designed and synthesized to competitively bind to the same DNA region as STAT3 in the PD-L1 promoter, downregulating PD-L1 expression and inducing apoptosis in tumor cells through Akt/caspase-3 pathway inhibition. Additionally, these polyamides enhanced T-cell-mediated killing of tumor cells and showed potential as PD-L1 gene-targeting antitumor drugs through immune and nonimmune pathways.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yuki Hirose, Shinsuke Sato, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: Compound 1 and its analogs 2-4 have been found to covalently bind to RUNX-binding sequences, inhibiting the binding of RUNX proteins to their target sites and suppressing cancer growth. Compound 3 showed the highest alkylation efficiency, specificity, and better anticancer effects against pancreatic cancer in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Junnosuke Hatanaka, Yuki Hirose, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: In this study, we synthesized linear pyrrole-imidazole polyamides (PIPs) that can selectively bind to DNA. These linear PIPs have lower molecular weights compared to commonly used hairpin PIPs. The binding affinity of the PIPs to DNA was improved by modifying the N-terminus of the linear PIPs. These findings provide insights for the design of effective linear PIPs.
Article
Oncology
Sakthisri Krishnamurthy, Hiroyuki Yoda, Kiriko Hiraoka, Takahiro Inoue, Jason Lin, Yoshinao Shinozaki, Takayoshi Watanabe, Nobuko Koshikawa, Atsushi Takatori, Hiroki Nagase
Summary: The novel pyrrole-imidazole polyamide-seco-CBI conjugate P3AE5K effectively targeted PIK3CA mutant cells in cervical cancer, demonstrating strong cytotoxicity and the potential to be a promising new drug candidate.
Article
Biochemistry & Molecular Biology
Conor T. Ronayne, Sravan K. Jonnalagadda, Shirisha Jonnalagadda, Grady L. Nelson, Lucas N. Solano, Hithardha Palle, Chinnadurai Mani, Jon Rumbley, Jon Holy, Venkatram R. Mereddy
Summary: CBISC, a novel nitrogen mustard, demonstrates enhanced inhibition of cell proliferation against certain cancer cell lines, and shows potential tumor growth inhibitory properties in both in vitro and in vivo studies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yuki Hirose, Tomo Ohno, Sefan Asamitsu, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: A cyclic pyrrole-imidazole polyamide (cPIP) was synthesized to bind to the abnormal expanded CAG/CTG repeat DNA sequences, showing high binding affinity and specificity for its target DNA sequence.
Article
Biochemistry & Molecular Biology
Junnosuke Hatanaka, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: A compound was synthesized to increase the transcription of the FXN gene in cells from FRDA patients at a lower concentration than previously reported. However, high concentrations of the compound are toxic, but toxicity can be reduced with a host-guest complex.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Meiqing Li, Danyi Lu, Yulian Cheng, Chunlei Wu, Jianchao Zhang, Wenli Shi, Zhihao Ding, Yanyan Li, Binghua Cheng, Xian Lin, Ximing Shao, Hongchang Li, Lijing Fang, Ke Liu, Wu Su
Summary: The newly developed drug molecule PIP-Ht targets the Aurora A gene promoter and shows potent inhibitory effects on tumor cell growth and proliferation in vitro and in vivo, demonstrating potential as an effective candidate for cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Nobuko Koshikawa, Yuki Kida, Nanami Yasui, Yoshinao Shinozaki, Kohei Tsuji, Takayoshi Watanabe, Jason Lin, Seigi Yamamoto, Keizo Takenaga, Hiroki Nagase
Summary: Somatic mutations in mitochondrial DNA present a potential avenue for cancer therapy, and short linear PI-TPPs demonstrate cytotoxic effects and induction of apoptosis in cells with A3243G mitochondrial mutations through targeted mitochondrial homing.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Eslam Dabbish, Stefano Scoditti, Mohammed N. I. Shehata, Ida Ritacco, Mahmoud A. A. Ibrahim, Tamer Shoeib, Emilia Sicilia
Summary: This paper presents a DFT investigation on the metabolic phases and cytotoxic mechanism of cyclophosphamide (CP). The computational analysis provides insights into the energy profiles and DNA alkylation mechanism, aiming to contribute to the design of a new generation of oxazaphosphorines.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yuki Mori, Hiroki Oi, Yuki Suzuki, Kumi Hidaka, Hiroshi Sugiyama, Masayuki Endo, Shigeyoshi Matsumura, Yoshiya Ikawa
Summary: Ribozymes with modular architecture have been designed, forming closed trimers and closed tetramers based on assembly of unit RNAs (L-RNAs). By tuning their structural elements, closed pentamers and closed hexamers were further extended, with their assembly properties analyzed using electrophoretic mobility shift assay (EMSA) and atomic force microscopy (AFM).
Article
Chemistry, Multidisciplinary
Junya Akagi, Takahiro Yamada, Kumi Hidaka, Yoshihiko Fujita, Hirohide Saito, Hiroshi Sugiyama, Masayuki Endo, Shigeyoshi Matsumura, Yoshiya Ikawa
Summary: Ribozymes are attractive platforms for constructing nanoscale objects with biological functions. In this study, a dimeric form of the Tetrahymena group I ribozyme was designed and analyzed biochemically and observed directly by atomic force microscopy. The formation of the ribozyme dimer triggered trans-splicing reactions, resulting in a fluorescent RNA aptamer as the trans-splicing product.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemical Research Methods
Takuya Hidaka, Wen Ann Wee, Ji Hye Yum, Hiroshi Sugiyama, Soyoung Park
Summary: This study induced phase transition of micro-compartments containing DNA and polylysine by modulating duplex formation of arylazopyrazole-conjugated oligonucleotides with light. UV irradiation destabilized DNA duplex and generated isotropic coacervates, while visible light irradiation caused the formation of liquid crystalline coacervates. This photocontrol of phase transition was highly repeatable, and similar changes were observed even after ten cycles of light irradiation.
BIOCONJUGATE CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Soumya Sethi, Hiroshi Sugiyama, Masayuki Endo
Summary: DNA nanotechnology is a promising toolkit for mimicking cell-cell and cell-matrix interactions, aiding in understanding and manipulating cellular functions. Future innovations in the field can be inspired by exploring the potentials of DNA-based nanostructures and addressing current challenges.
Article
Biochemistry & Molecular Biology
Yuki Hirose, Tomo Ohno, Sefan Asamitsu, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: A cyclic pyrrole-imidazole polyamide (cPIP) was synthesized to bind to the abnormal expanded CAG/CTG repeat DNA sequences, showing high binding affinity and specificity for its target DNA sequence.
Article
Biochemistry & Molecular Biology
Ryu Tashiro, Ji Hye Yum, Soyoung Park, Hiroshi Sugiyama
Summary: The study showed that the photoreactivity of U-Br changes dramatically from hydrogen abstraction to cross-linking by changing the conformation of the duplex from the B-form to the A-form. Among three A-form structures, the largest amount of cross-linked products was observed when U-Br was incorporated into the RNA strand and the pyrene was conjugated to the 5 ' end of the DNA. These results indicate that the contact manner of pyrene was different between A- and B-form duplexes.
Article
Biochemistry & Molecular Biology
Kai Yu, Kumi Hidaka, Hiroshi Sugiyama, Masayuki Endo, Shigeyoshi Matsumura, Yoshiya Ikawa
Summary: Naturally occurring ribozymes with modular architecture are promising for designing and assembling three-dimensional RNA nanostructures with catalytic abilities. In this study, RNA nanostructures with polygonal-shaped ribozyme oligomers were constructed using unit RNAs from the Tetrahymena group I intron, and ribozyme trimers with a triangular shape were dimerized by introducing pillar units. The resulting double-decker nanostructures containing six ribozyme units showed higher catalytic activity than the parent ribozyme trimers.
Article
Biochemistry & Molecular Biology
Sagun Jonchhe, Shankar Pandey, Christian Beneze, Tomoko Emura, Hiroshi Sugiyama, Masayuki Endo, Hanbin Mao
Summary: Researchers found that a DNA nanobowl significantly increased the stability of a human telomeric G-quadruplex and its binding with a ligand. By minimizing the proximity effect and attributing the increased affinity to the nanoconfinement effect, they provided insights into the mechanisms of binding events in nanocavities.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Vinodh J. Sahayasheela, Zutao Yu, Yuki Hirose, Ganesh N. Pandian, Toshikazu Bando, Hiroshi Sugiyama
Summary: Research suggests that targeting Gli-mediated transcription to inhibit the proliferation of cancer stem cells may be a promising strategy.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Biochemistry & Molecular Biology
Shingo Hirashima, Hiroshi Sugiyama, Soyoung Park
Summary: This study characterized 2FA-containing DNA molecules and found that they have similar structure and properties to native adenine due to their small size, but exhibit unique features due to their high electronegativity. This provides valuable information for future applications of 2FA-modified DNA.
Article
Biochemistry & Molecular Biology
Junnosuke Hatanaka, Yuki Hirose, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
Summary: In this study, we synthesized linear pyrrole-imidazole polyamides (PIPs) that can selectively bind to DNA. These linear PIPs have lower molecular weights compared to commonly used hairpin PIPs. The binding affinity of the PIPs to DNA was improved by modifying the N-terminus of the linear PIPs. These findings provide insights for the design of effective linear PIPs.
Article
Materials Science, Multidisciplinary
Atsushi Nakayama, Yasuaki Kumamoto, Masafumi Minoshima, Kazuya Kikuchi, Atsushi Taguchi, Katsumasa Fujita
Summary: This study demonstrates the use of photopolymerization without photoinitiators to fabricate 3D structures using biocompatible materials. The material properties of poly(ethylene glycol) diacrylate (PEGda) and collagen are preserved, making them suitable for applications with live cells.
ADVANCED OPTICAL MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Masafumi Minoshima, Taro Umeno, Kohei Kadooka, Margaux Roux, Namiko Yamada, Kazuya Kikuchi
Summary: To understand protein function in live cells, it is important to monitor protein dynamics and sense their environment in real-time. We developed a versatile chemical protein-labeling tool that efficiently forms stable carbamoylated complexes with beta-lactamase, allowing long-term visualization of labeled proteins in live cells. The use of an alpha-fluorinated carboxylate ester-based prodrug enables cell membrane permeability and stable labeling of intracellular proteins. Combining this labeling tool with a pH-activatable fluorescent probe enables visual monitoring of lysosomal protein translocation during autophagy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ryu Hashimoto, Masafumi Minoshima, Souhei Sakata, Fumihito Ono, Hirokazu Ishii, Yuki Watakabe, Tomomi Nemoto, Saeko Yanaka, Koichi Kato, Kazuya Kikuchi
Summary: In this study, visible-light-sensitive protecting groups with high uncaging cross sections were developed for precise control of bioactivity. Two-photon photolysis reactions were achieved using near-infrared laser, and green-light illumination enabled optical control of biological functions.
Article
Biochemistry & Molecular Biology
Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Ganesh N. Pandian, Hiroshi Sugiyama
Summary: This study constructed a class of compounds that can selectively alkylate mutant mitochondrial DNA, with the potential to treat mitochondrial diseases. These compounds have programmability and can be used to target pathogenic mutations associated with mitochondrial diseases in future studies.
CELL CHEMICAL BIOLOGY
(2022)
