Papers - USUI Kenji
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Design of anti-alzheimer’s disease agents focusing on a specific interaction with target biomolecules Reviewed
Yoshio Hamada, Kenji Usui
Neuromethods 132 207 - 228 2018
Joint Work
Publisher：Humana Press Inc.
Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive intellectual deterioration. Amyloid β peptide (Aβ), the main component of senile plaques in the brains of patients with AD, is formed from amyloid precursor protein (APP) by two processing enzymes. According to the amyloid hypothesis, a processing enzyme β-secretase (BACE1
β-site APP cleaving enzyme) that triggers Aβ formation in the rate-limiting first step of Aβ processing appears to be a promising molecular target for therapeutic intervention in AD. Many researchers have revealed BACE1 inhibitors for the AD treatment. Early BACE1 inhibitors were designed based on the first reported X-ray crystal structure, 1FKN, of a complex between recombinant BACE1 and inhibitor OM99-2. Although OM99-2 seemed to interact with BACE1-Arg235 side chain by hydrogen bonding, we found that a quantum chemical interaction, such as σ-π interaction or π-π stacking, plays a critical role in BACE1 inhibition mechanism. Moreover, we proposed a novel “electron-donor bioisostere” concept in drug discovery study and designed potent BACE1 inhibitors using this concept. -
Channel current analysis estimates the pore-formation and the penetration of transmembrane peptides Reviewed
Sekiya, Y., Sakashita, S., Shimizu, K., Usui, K., Kawano, R.
Analyst 143 ( 15 ) 2018
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生体分子の挙動解析研究を目標としたマイクロ波照射システムの開発 ～ペプチドのバイオミネラリゼーションにおけるマイクロ波影響解析をモデルとして～ Reviewed
臼井健二, 富樫浩行, 圓東那津実, 尾崎誠, 有本米次郎, 裏鍛武史, 大沢隆二, 皆木幸一, 中西伸浩, 梅谷智弘
日本電磁波エネルギー応用学会論文誌 17 - 24 2017.12
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Non-Covalent Loading of Anti-Cancer Doxorubicin by Modularizable Peptide Self-Assemblies for a Nanoscale Drug Carrier Reviewed
Kin-ya Tomizaki, Kohei Kishioka, Shunsuke Kataoka, Makoto Miyatani, Takuya Ikeda, Mami Komada, Takahito Imai, Kenji Usui
MOLECULES 22 ( 11 ) 1916 2017.11
Joint Work
Authorship：Lead author Publisher：MDPI AG
We prepared nanoscale, modularizable, self-assembled peptide nanoarchitectures with diameters less of than 20 nm by combining beta-sheet-forming peptides tethering a cell-penetrating peptide or a nuclear localization signal sequence. We also found that doxorubicin (Dox), an anti-cancer drug, was non-covalently accommodated by the assemblies at a ratio of one Dox molecule per ten peptides. The Dox-loaded peptide assemblies facilitated cellular uptake and subsequent nuclear localization in HeLa cells, and induced cell death even at low Dox concentrations. This peptide nanocarrier motif is a promising platform for a biocompatible drug delivery system by altering the targeting head groups of the carrier peptides.
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DNA G-Wire Formation Using an Artificial Peptide is Controlled by Protease Activity Reviewed
Kenji Usui, Arisa Okada, Shungo Sakashita, Masayuki Shimooka, Takaaki Tsuruoka, Shu-ichi Nakano, Daisuke Miyoshi, Tsukasa Mashima, Masato Katahira, Yoshio Hamada
MOLECULES 22 ( 11 ) 1991 2017.11
Joint Work
Authorship：Lead author Publisher：MDPI AG
The development of a switching system for guanine nanowire (G-wire) formation by external signals is important for nanobiotechnological applications. Here, we demonstrate a DNA nanostructural switch (G-wire <--> particles) using a designed peptide and a protease. The peptide consists of a PNA sequence for inducing DNA to form DNA-PNA hybrid G-quadruplex structures, and a protease substrate sequence acting as a switching module that is dependent on the activity of a particular protease. Micro-scale analyses via TEM and AFM showed that G-rich DNA alone forms G-wires in the presence of Ca2+, and that the peptide disrupted this formation, resulting in the formation of particles. The addition of the protease and digestion of the peptide regenerated the G-wires. Macro-scale analyses by DLS, zeta potential, CD, and gel filtration were in agreement with the microscopic observations. These results imply that the secondary structure change (DNA G-quadruplex <--> DNA/PNA hybrid structure) induces a change in the well-formed nanostructure (G-wire <--> particles). Our findings demonstrate a control system for forming DNA G-wire structures dependent on protease activity using designed peptides. Such systems hold promise for regulating the formation of nanowire for various applications, including electronic circuits for use in nanobiotechnologies.
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Fluorescent and luminescent fusion proteins for analyses of amyloid beta peptide aggregation Reviewed
Kenji Usui, Masayasu Mie, Takashi Andou, Hisakazu Mihara, Eiry Kobatake
JOURNAL OF PEPTIDE SCIENCE 23 ( 7-8 ) 659 - 665 2017.7
Joint Work
Authorship：Lead author Publisher：WILEY
The amyloid beta (A) peptide is regarded as a causative agent of Alzheimer's disease. In this study, fluorescent and luminescent fusion proteins were constructed to analyze A aggregation. A system was developed to monitor changes in luminescence that provides information about A aggregation. In the presence of monomeric A, the fusion protein exhibits higher luminescence intensity, and the luminescence intensity is diminished after aggregation of the fusion protein and A. In contrast, the fluorescence is sustained in the presence of A. In the absence of A, the fusion protein self-aggregates, and its luminescence and fluorescence are quenched, thus decreasing the background fluorescence and enhancing the detection of A inside and outside the cells. The ratio of the luminescence intensity to the fluorescence intensity would allow the aggregation degrees of A to be distinguished. This study would be a promising method for analyzing the aggregation state of a particular amyloid protein/peptide (monomer, oligomer, or fibril), as well as the distribution of the amyloid protein/peptide within and at the cell surface, by using a single fusion protein. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
DOI： 10.1002/psc.3003
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Development of Peptide Microarray to Detect the Protein in Saliva for Periodontal Disease Test Reviewed
Yuki Tominaga, Kenji Usui, Akiyoshi Hirata, Atsushi Kitagawa, Hiro-O Ito and Kiyoshi Nokihara
Peptide Science 2016 131 - 132 2017.3
Joint Work
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A Systematic Study on Molecular Mechanism of Pore-Forming Peptides for Discovering Antimicrobial Medicine
Y. Sekiya, H. Watanabe, K. Usui, R. Kawano
Proceedings of MicroTAS 2016 595 - 596 2016.10
Joint Work
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Site-Specific Control of Silica Mineralization on DNA Using a Designed Peptide Reviewed
M. Ozaki, K. Nagai, H. Nishiyama, T. Tsuruoka, S. Fujii, T. Endoh, T. Imai, K.-y. Tomizaki, K. Usui
Chem. Commun. 52 4010 - 4013 2016.3
Joint Work
Authorship：Lead author
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Development of Designed Peptides with Secondary Structure for Use in Nanobiotechnology Invited Reviewed
K.Usui
Peptide Science 2015 5 - 8 2016.3
Single Work
Authorship：Lead author
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A Cell Microarray Format: A Peptide Release System Using a Photo-Cleavable Linker for Cell Toxicity and Cell Uptake Analysis. Reviewed
Usui K, Tomizaki KY, Mihara H
Methods in molecular biology (Clifton, N.J.) 1352 199 - 210 2016
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Site-specific control of multiple mineralizations using a designed peptide and DNA Reviewed
Kenji Usui, Makoto Ozaki, Aoi Yamada, Yoshio Hamada, Takaaki Tsuruoka, Takahito Imai, Kin-ya Tomizaki
NANOSCALE 8 ( 39 ) 17081 - 17084 2016
Publisher：ROYAL SOC CHEMISTRY
We have developed a site-specific method for precipitating multiple inorganic compounds using target DNA and a designed peptide consisting of a peptide nucleic acid (PNA) sequence and an inorganic compound-precipitating sequence. This system for controlled site-specific precipitation represents a powerful tool for use in nanobiotechnology and materials science.
DOI： 10.1039/c6nr03468c
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Site-specific control of silica mineralization on DNA using a designed peptide Reviewed
Makoto Ozaki, Kazuma Nagai, Hiroto Nishiyama, Takaaki Tsuruoka, Satoshi Fujii, Tamaki Endoh, Takahito Imai, Kin-ya Tomizaki, Kenji Usui
CHEMICAL COMMUNICATIONS 52 ( 21 ) 4010 - 4013 2016
Publisher：ROYAL SOC CHEMISTRY
We developed a site-specific method for precipitating inorganic compounds using organic compounds, DNA, and designed peptides with peptide nucleic acids (PNAs). Such a system for site-specific precipitation represents a powerful tool for use in nanobiochemistry and materials chemistry.
DOI： 10.1039/c5cc07870a
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ATP-Binding Peptide-Hydrogel Composite Synthesized by Molecular Imprinting on Beads Reviewed
Ayana Takata, Kenji Usui, Jun Matsui
Molecular Imprinting 3 65 - 70 2015.12
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A Cell Microarray Format: A Peptide Release System Using a Photo-Cleavable Linker for Cell Toxicity and Cell Uptake Analysis Reviewed
K. Usui, K.-y. Tomizaki, H. Mihara
Methods. Mol. Biol. 1352 199 - 210 2015.11
Joint Work
Authorship：Lead author
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Label and Label-Free Detection Techniques for Protein Microarrays. Reviewed International coauthorship
Syahir A, Usui K, Tomizaki KY, Kajikawa K, Mihara H
Microarrays (Basel, Switzerland) 4 ( 4 ) 228 - 244 2015.4
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Site-Specific Mineralization of Silica and Calcium on DNAs Using a Designed Peptide Reviewed
K. Usui, H. Nishiyama, A. Yamada, M. Ozaki, T. Tsuruoka, K.-y. Tomizaki
Peptide science 2014 325 - 326 2015.3
Joint Work
Authorship：Lead author
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Control of guanine-rich DNA secondary structures depending on the protease activity using a designed PNA peptide Reviewed
Kenji Usui, Arisa Okada, Keita Kobayashi, Naoki Sugimoto
ORGANIC & BIOMOLECULAR CHEMISTRY 13 ( 7 ) 2022 - 2025 2015
Publisher：ROYAL SOC CHEMISTRY
We constructed a regulation system for DNA secondary structure formation of G-rich sequences using a designed PNA peptide exhibiting an on-to-off switching functionality, depending on the protease activity. This study introduces the new concept of a simple and powerful system for regulating quadruplex-related important biological events.
DOI： 10.1039/c4ob02535k
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Cellular differentiation assessments by measuring the degree of cellular internalization and membrane adsorption using designed peptides Reviewed
Kenji Usui, Takuya Kikuchi, Kunio Kikuchi, Masayasu Mie, Eiry Kobatake, Hisakazu Mihara
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24 ( 17 ) 4129 - 4131 2014.9
Publisher：PERGAMON-ELSEVIER SCIENCE LTD
We demonstrate examples of cellular differentiation assessments, including cellular neurite outgrowth and fat cell maturation, by measuring the degree of membrane adsorption or cellular internalization using designed peptides. Because changes in the cellular membrane and cytosol during differentiation were shown to influence membrane adsorption and cellular internalization, we could successfully evaluate the extent of differentiation simply like stain indicators. (C) 2014 Elsevier Ltd. All rights reserved.
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A Designed Small Protein For Controlling Site-Specific Mineralization Of Silica And Calcium On Dnas Reviewed
Kenji Usui, Kazuma Nagai, Hiroto Nishiyama, Aoi Yamada, Makoto Ozaki, Takaaki Tsuruoka, Kin-ya Tomizaki
PROTEIN SCIENCE 23 143 - 143 2014.7