論文 - 松原　輝彦

A Photoresponsive Hybrid of Viruses and Supramolecular Peptide Fibers for Multidimensional Control of Patterning and Infection

Yaguchi A., Uchida N., Miura D., Watanabe G., Hiramatsu H., Ajioka I., Matsubara T., Sato T., Enkhzaya C., Itani S., Saito T., Muraoka T.

Angewandte Chemie International Edition 64 （ 41 ）  2025年10月

ISSN  14337851

　概要を見る

Viruses are versatile colloidal materials in their biofunctions, monodispersed and periodic structures, and high surface designability. For expanding the applicability of virus-based materials, spatiotemporally controlled immobilization and dispersion of viruses with retained activity should be useful, though control of the dynamic nature of viruses hybridized with commonly used polymers has been difficult due to their strong interactions. Here, we report a self-assembling peptide (A2Az) enabling photo control of adhesion and dispersion of M13 bacteriophage virus (M13 phage) and successfully demonstrate patterning of localization and infection of the virus. A2Az is a cationic peptide with amphiphilicity that consists of eight amino acid residues containing a photo-responsive azobenzene group at the second position and self-assembles into a helical supramolecular fiber to form a hydrogel. The helical fibrillar morphology of A2Az exhibits strong interaction with M13 phage, allowing for immobilization not only on a two-dimensional surface but also in a three-dimensional hydrogel with suppression of infectivity. The A2Az fiber undergoes a light-triggered fiber-to-particle transition and releases the immobilized M13 phage with retained infectivity for the photo-controlled patterning of localization and infection. This approach has potential applicability to various virus-based biomaterials, such as structural materials and materials for photo-selective gene transfection to cells.

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Prevention of amyloid β fibril deposition on the synaptic membrane in the precuneus by ganglioside nanocluster-targeting inhibitors

Miyamoto E., Hayashi H., Murayama S., Yanagisawa K., Sato T., Matsubara T.

Rsc Chemical Biology 5 （ 5 ） 459 - 466 2024年04月

　概要を見る

Alzheimer's disease (AD), a progressive neurodegenerative condition, is one of the most common causes of dementia. Senile plaques, a hallmark of AD, are formed by the accumulation of amyloid β protein (Aβ), which starts to aggregate before the onset of the disease. Gangliosides, sialic acid-containing glycosphingolipids, play a key role in the formation of toxic Aβ aggregates. In membrane rafts, ganglioside-bound complexes (GAβ) act as nuclei for Aβ assembly, suggesting that GAβ is a promising target for AD therapy. The formation of GAβ-induced Aβ assemblies has been evaluated using reconstituted planar lipid membranes composed of synaptosomal plasma membrane (SPM) lipids extracted from human and mouse brains. Although the effects of gangliosides on Aβ accumulation in the precuneus have been established, effects on Aβ fibrils have not been determined. In this study, Aβ<inf>42</inf> fibrils on reconstituted membranes composed of SPM lipids prepared from the precuneus cortex of human autopsied brains were evaluated by atomic force microscopy. In particular, Aβ<inf>42</inf> accumulation, as well as the fibril number and size were higher for membranes with precuneus lipids than for membranes with calcarine cortex lipids. In addition, artificial peptide inhibitors targeting Aβ-sensitive ganglioside nanoclusters cleared Aβ assemblies on synaptic membranes in the brain, providing a novel therapeutic strategy for AD.

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Cyclization of Peptides Enhances the Inhibitory Activity against Ganglioside-Induced Aβ Fibril Formation

Miyamoto E., Sato T., Matsubara T.

ACS Chemical Neuroscience 14 （ 23 ） 4199 - 4207 2023年12月

　概要を見る

Alzheimer’s disease is a progressive neurodegenerative disease and is the most common cause of dementia. It has been reported that the assembly of amyloid β-protein (Aβ) on the cell membrane is induced by the interaction of the Aβ monomer with gangliosides such as GM1. The ganglioside-bound Aβ (GAβ) complex acts as a seed to promote the toxic assembly of the Aβ fibrils. In a previous study, we found that a GM1 cluster-binding peptide (GCBP) specifically recognizes Aβ-sensitive ganglioside nanoclusters and inhibits the assembly of Aβ on a GM1-containing lipid membrane. In this study, cysteine-substituted double mutants of GCBP were designed and cyclized by intramolecular disulfide bond formation. Affinity assays indicated that one of the cyclic peptides had a higher affinity to a GM1-containing membrane compared to that of GCBP. Furthermore, surface topography analysis indicated that this peptide recognizes GM1 nanoclusters on the lipid membrane. An evaluation of the inhibitory kinetics indicated that the cyclic peptide could inhibit the formation of Aβ fibrils with an IC<inf>50</inf> value of 1.2 fM, which is 10,000-fold higher than that of GCBP. The cyclic peptide was also shown to have a clearance effect on Aβ fibrils deposited on the lipid membrane and suppressed the formation of toxic Aβ assemblies. Our results indicate that the cyclic peptide that binds to the Aβ-sensitive ganglioside nanocluster is a potential novel inhibitor of ganglioside-induced Aβ assembly.

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Effects of the Magnetic Orientation of M13 Bacteriophage on Phage Display Selection

Wang S., Uchida N., Ueno K., Matsubara T., Sato T., Aida T., Ishida Y.

Chemistry A European Journal 29 （ 63 ）  2023年11月

ISSN  09476539

　概要を見る

Although phage display selection using a library of M13 bacteriophage has become a powerful tool for finding peptides that bind to target materials on demand, a remaining concern of this method is the interference by the M13 main body, which is a huge filament >10³ times larger than the displayed peptide, and therefore would nonspecifically adhere to the target or sterically inhibit the binding of the displayed peptide. Meanwhile, filamentous phages are known to be orientable by an external magnetic field. If M13 filaments are magnetically oriented during the library selection, their angular arrangement relative to the target surface would be changed, being expected to control the interference by the M13 main body. This study reports that the magnetic orientation of M13 filaments vertical to the target surface significantly affects the selection. When the target surface was affinitive to the M13 main body, this orientation notably suppressed the nonspecific adhesion. Furthermore, when the target surface was less affinitive to the M13 main body and intrinsically free from the nonspecific adhesion, this orientation drastically changed the population of M13 clones obtained through library selection. The method of using no chemicals but only a physical stimulus is simple, clean, and expected to expand the scope of phage display selection.

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Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery

Uchida N., Ryu Y., Takagi Y., Yoshizawa K., Suzuki K., Anraku Y., Ajioka I., Shimokawa N., Takagi M., Hoshino N., Akutagawa T., Matsubara T., Sato T., Higuchi Y., Ito H., Morita M., Muraoka T.

Journal of the American Chemical Society 145 （ 11 ） 6210 - 6220 2023年03月

ISSN  00027863

　概要を見る

Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.

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Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

Saito S., Funayama K., Kato W., Okuda M., Kawamoto M., Matsubara T., Sato T., Sato A., Otsuguro S., Sasaki M., Orba Y., Sawa H., Maenaka K., Shindo K., Imoto M., Arai M.A.

Journal of Natural Products 85 （ 11 ） 2583 - 2591 2022年11月

ISSN  01633864

　概要を見る

Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC<inf>50</inf>values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC<inf>50</inf>values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC<inf>50</inf>concentrations.

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Effective Cell Transfection in An Ultrasonically Levitated Droplet for Sustainable Technology

Arai T., Sato T., Matsubara T.

Advanced Science 9 （ 30 ）  2022年10月

　概要を見る

The levitation methodology, which enables us to operate a contactless reaction without a container, is likely to be a revolutionary technology in the fields of chemistry and biology to reduce the plastic waste in life science laboratories. Here, the authors show that plasmid DNA can be effectively transfected into animal cells in a floating droplet of culture medium levitated using ultrasonic standing waves. The data indicate that there is no significant damage to the plasmid and cells during the levitating transfection time, and the transgene expression efficiency and cellular uptake in the droplet are significantly higher than those in the conventional tube, with and without shaking. These results suggest the consolidation of the endocytic uptake pathway into macropinocytosis, indicating that ultrasonic levitation induced a change in cell characteristics. This study suggests that transfection methodology using ultrasonic levitation has the potential to advance the current experimental procedures in the field of cell engineering, in addition to presenting a revolutionary containerless reactor for sustainable technology.

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Peptide mimotopes to emulate carbohydrates

Matsubara T.

Chemical Society Reviews 51 （ 19 ） 8160 - 8173 2022年09月

ISSN  03060012

　概要を見る

Glycoconjugates on animal cell surfaces are involved in numerous biological functions and diseases, especially the adhesion/metastasis of cancer cells, infection, and the onset of glycan-related diseases. In addition to glycoantigen detection, the regulation of glycan (carbohydrate)-protein interactions is needed to develop therapeutic strategies for glycan-related diseases. Preparation of a diverse range of glycan derivatives requires a massive effort, but the preparation and identification of alternative glycan-mimetic peptide mimotopes may provide a solution to this issue. Peptide mimotopes are recognized by glycan-binding proteins, such as lectins, enzymes, and antibodies, alternative to glycan ligands. Phage-display technology is the first choice in the selection of “glycan (carbohydrate)-mimetic peptide mimotopes” from a large repertoire of library sequences. This tutorial review describes the advantages of peptide mimotopes in comparison to glycan ligands, as well as their structural and functional mimicry. The detailed library design is followed by a description of the strategy used to improve affinity, and finally, an outline of the vaccine application of glycan-mimetic peptides is provided.

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Ganglioside Nanocluster-Targeting Peptidyl Inhibitor Prevents Amyloid β Fibril Formation on the Neuronal Membrane

Matsubara T., Nakai M., Nishihara M., Miyamoto E., Sato T.

ACS Chemical Neuroscience 13 （ 13 ） 1868 - 1876 2022年07月

　概要を見る

Neurotoxicity caused by peptide and protein aggregates is associated with the onset of neurodegenerative diseases. Accumulation of the amyloid β protein (Aβ) induced by neuronal ganglioside-enriched nanodomains (nanoclusters) in the presynaptic neuronal membrane, resulting in toxic oligomeric and fibrous forms, is implicated in the onset of Alzheimer's disease (AD). In the current study, we found that the ganglioside cluster-binding peptide (GCBP), a pentadecapeptide VWRLLAPPFSNRLLP that binds to ganglioside-enriched nanoclusters, inhibits the formation of Aβ assemblies with an IC50 of 12 pM and also removes Aβ fibrils deposited on the lipid membrane. Thus, in addition to inhibiting Aβ assembly formation, GCBP effectively clears toxic Aβ assemblies as well, thereby suppressing neuronal cellular damage and death induced by such assemblies. These results indicate that ganglioside cluster-binding molecules may act as novel Aβ-targeting drugs with a unique mechanism of action that may be utilized to ameliorate AD.

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Detection of Influenza Virus by Agglutination of Microparticles Immobilized a Mixed Glycan Receptor Produced from Cells

Matsubara T., Ogami A., Kori H., Hashizume M., Sato T.

ACS Applied Bio Materials （ACS Applied Bio Materials）  5 （ 5 ） 2130 - 2134 2022年05月

　概要を見る

The hemagglutination inhibition (HAI) assay is one of the detection methods for influenza virus (IFV) under global influenza surveillance, which uses freshly prepared animal red blood cells (RBCs). Here, we demonstrate that a mixed glycan-modified polystyrene microparticle, which can be chemically prepared in advance, can replace animal RBCs in the HAI assay. A mixture of azide-conjugated glycans containing sialyl- and sulfated-lactose moieties was produced from Madin-Darby canine kidney (MDCK) cells, which are used for IFV isolation, and then immobilized on the surface of a polystyrene microparticle using click chemistry. Human HA and IFV were detected with high sensitivity when using the mixed glycan-immobilized particle.

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De Novo Design of Star-Shaped Glycoligands with Synthetic Polymer Structures toward an Influenza Hemagglutinin Inhibitor

Nagao M., Yamaguchi A., Matsubara T., Hoshino Y., Sato T., Miura Y.

Biomacromolecules （Biomacromolecules）  23 （ 3 ） 1232 - 1241 2022年03月

ISSN  15257797

　概要を見る

Synthetic polymers with well-defined structures allow the development of nanomaterials with additional functions beyond biopolymers. Herein, we demonstrate de novo design of star-shaped glycoligands to interact with hemagglutinin (HA) using well-defined synthetic polymers with the aim of developing an effective inhibitor for the influenza virus. Prior to the synthesis, the length of the star polymer chains was predicted using the Gaussian model of synthetic polymers, and the degree of polymerization required to achieve multivalent binding to three carbohydrate recognition domains (CRDs) of HA was estimated. The star polymer with the predicted degree of polymerization was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, and 6′-sialyllactose was conjugated as the glycoepitope for HA. The designed glycoligand exhibited the strongest interaction with HA as a result of multivalent binding. This finding demonstrated that the biological function of the synthetic polymer could be controlled by precisely defining the polymer structures.

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Motobamide, an Antitrypanosomal Cyclic Peptide from a Leptolyngbya sp. Marine Cyanobacterium

Takahashi H., Iwasaki A., Kurisawa N., Suzuki R., Jeelani G., Matsubara T., Sato T., Nozaki T., Suenaga K.

Journal of Natural Products （Journal of Natural Products）  84 （ 5 ） 1649 - 1655 2021年05月

ISSN  01633864

　概要を見る

Motobamide (1), a new cyclic peptide containing a C-prenylated cyclotryptophan residue, was isolated from a marine Leptolyngbya sp. cyanobacterium. Its planar structure was established by spectroscopic and MS/MS analyses. The absolute configuration was elucidated based on a combination of chemical degradations, chiral-phase HPLC analyses, spectroscopic analyses, and computational chemistry. Motobamide (1) moderately inhibited the growth of bloodstream forms of Trypanosoma brucei rhodesiense (IC50 2.3 μM). However, it exhibited a weaker cytotoxicity against normal human cells (IC50 55 μM).

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Containerless Bioorganic Reactions in a Floating Droplet by Levitation Technique Using an Ultrasonic Wave

Matsubara T., Takemura K.

Advanced Science （Advanced Science）  8 （ 3 ）  2021年02月

　概要を見る

To ensure sustainable consumption and production patterns, alternative process design without plastics for chemical and biological reactions will benefit future generations. Reaction flasks used in chemical and biological laboratories have been made from glass, metals, and plastics so far. If containerless processing can be realized, researchers will have a next-generation reaction process, which will be reactor and plastic-free, and without risks of unforeseen issues induced by contact with reactions flasks, including contamination and alteration of the reactants. Here, polymerization, click chemistry, and enzymatic reactions can proceed effectively in a floating droplet at a node of standing wave generated by ultrasonic levitation. These results demonstrate that floating droplets levitated by acoustic waves can represent a revolutionary containerless reactor for performing various reactions in the fields of chemistry and biology.

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Heterogeneous Ganglioside-Enriched Nanoclusters with Different Densities in Membrane Rafts Detected by a Peptidyl Molecular Probe

Matsubara T., Iijima K., Kojima T., Hirai M., Miyamoto E., Sato T.

Langmuir （Langmuir）  37 （ 2 ） 646 - 654 2021年01月

ISSN  07437463

　概要を見る

The specific features of the lateral distribution of gangliosides play key roles in cell-cell communications and the onset of various diseases related to the plasma membrane. We herein demonstrated that an artificial peptide identified from a phage-displayed library is available as a molecular probe for specific ganglioside nanoclustering sites in caveolae/membrane rafts on the cell surface. Atomic force microscopy studies indicated that the peptide specifically binds to the highly enriched monosialoganglioside GM1 nanodomains of reconstituted lipid bilayers composed of GM1, sphingomyelin, cholesterol, and unsaturated phospholipids. The ganglioside-containing area recognized by the peptide on the surface of PC12 cells was part of the area recognized by the cholera toxin B subunit, which has high affinity for GM1. Furthermore, the peptide bound to the cell surface after a treatment with methyl-β-cyclodextrin (MβCD), which disrupts membrane rafts by removing cholesterol. The present results indicate that there are heterogeneous ganglioside clusters with different ganglioside densities in caveolae/membrane rafts, and the peptidyl probe selectively recognizes the high-density ganglioside nanodomain that resists the MβCD treatment. This peptidyl probe will be useful for obtaining information on the lipid organization of the cell membrane and will help clarify the mechanisms by which the lateral distribution of gangliosides affects biological functions and the onset of diseases.

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Ikoamide, an Antimalarial Lipopeptide from an Okeania sp. Marine Cyanobacterium

Iwasaki K., Iwasaki A., Sumimoto S., Matsubara T., Sato T., Nozaki T., Saito-Nakano Y., Suenaga K.

Journal of Natural Products （Journal of Natural Products）  83 （ 2 ） 481 - 488 2020年02月

ISSN  01633864

　概要を見る

An antimalarial lipopeptide, ikoamide, was isolated from an Okeania sp. marine cyanobacterium. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral-phase HPLC analyses, spectroscopic analyses, and derivatization reactions. Ikoamide showed strong antimalarial activity with an IC50 value of 0.14 μM without cytotoxicity against human cancer cell lines at 10 μM.

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Avian Influenza Virus Detection by Optimized Peptide Termination on a Boron-Doped Diamond Electrode

Matsubara T., Ujie M., Yamamoto T., Einaga Y., Daidoji T., Nakaya T., Sato T.

ACS Sensors （ACS Sensors）  5 （ 2 ） 431 - 439 2020年02月

　概要を見る

The development of a simple detection method with high sensitivity is essential for the diagnosis and surveillance of infectious diseases. Previously, we constructed a sensitive biosensor for the detection of pathological human influenza viruses using a boron-doped diamond electrode terminated with a sialyloligosaccharide receptor-mimic peptide that could bind to hemagglutinins involved in viral infection. Circulation of influenza induced by the avian virus in humans has become a major public health concern, and methods for the detection of avian viruses are urgently needed. Here, peptide density and dendrimer generation terminated on the electrode altered the efficiency of viral binding to the electrode surface, thus significantly enhancing charge-transfer resistance measured by electrochemical impedance spectroscopy. The peptide-terminated electrodes exhibited an excellent detection limit of less than one plaque-forming unit of seasonal H1N1 and H3N2 viruses. Furthermore, the improved electrode was detectable for avian viruses isolated from H5N3, H7N1, and H9N2, showing the potential for the detection of all subtypes of influenza A virus, including new subtypes. The peptide-based electrochemical architecture provided a promising approach to biosensors for ultrasensitive detection of pathogenic microorganisms.

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Detection of influenza virus by agglutination using nanoparticles conjugated with a sialic acid-mimic peptide

Matsubara T., Kubo A., Sato T.

Polymer Journal （Polymer Journal）  52 （ 2 ） 261 - 266 2020年02月

ISSN  00323896

　概要を見る

Abstract: Influenza virus (IFV) detection in the early phase of disease is critical for effective anti-influenza therapy using neuraminidase inhibitors. Sialyloligosaccharide receptors on the surface of respiratory cells are recognized by IFV hemagglutinin (HA) in the infection. Here, we show that agglutination of IFV is detected using poly(glycidyl methacrylate) (PGMA)-coated polystyrene nanoparticles conjugated with a sialic acid-mimic peptide. The azido peptide was immobilized onto the surface of the PGMA-coated nanoparticles by click chemistry. The distribution of particle size, determined by dynamic light scattering, indicated that the peptide-conjugated nanoparticles were agglutinated in the presence of HA and IFV. Nanoparticles conjugated with the receptor-mimic peptide may be a useful alternative to red blood cells in the global surveillance and clinical diagnosis of influenza.

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Synthesis of Various Glycopolymers Bearing Sialyllactose and the Effect of Their Molecular Mobility on Interaction with the Influenza Virus

Nagao M., Matsubara T., Hoshino Y., Sato T., Miura Y.

Biomacromolecules （Biomacromolecules）  20 （ 7 ） 2763 - 2769 2019年07月

ISSN  15257797

　概要を見る

Synthetic glyco-ligands are promising candidates for effective nanomedicines against pathogens. Glycopolymers bearing sialyl-oligosaccharides interact with hemagglutinin present on the surface of influenza viruses. In designing new glycopolymers that further enhance the interaction with viruses, both static and dynamic properties of the glycopolymers should be considered. In this report, we evaluated the correlation between dynamic properties of glycopolymers and their interaction with the influenza virus. Glycopolymers with pendant sialyllactoses and various linker structures were synthesized, and their molecular mobility was determined by proton spin-spin relaxation time measurements. The molecular mobility of the glycounits increased as the length of the linker structures increased. Interestingly, glycopolymers with the medium-length linker structure exhibited the strongest interaction with the influenza virus, suggesting that optimal molecular mobility is required for maximizing multivalent interactions with the target.

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Topological Design of Star Glycopolymers for Controlling the Interaction with the Influenza Virus

Nagao M., Matsubara T., Hoshino Y., Sato T., Miura Y.

Bioconjugate Chemistry （Bioconjugate Chemistry）  30 （ 4 ） 1192 - 1198 2019年04月

ISSN  10431802

　概要を見る

The precise design of synthetic polymer ligands using controlled polymerization techniques provides an advantage for the field of nanoscience. We report the topological design of glyco-ligands based on synthetic polymers for targeting hemagglutinin (HA, lectin on the influenza virus). To achieve precise arrangement of the glycounits toward the sugar-binding pockets of HA, triarm star glycopolymers were synthesized. The interaction of the star glycopolymers with HA was found to depend on the length of the polymer arms and was maximized when the hydrodynamic diameter of the star glycopolymer was comparable to the distance between the sugar-binding pockets of HA. Following the formula of multivalent interaction, the number of binding sites in the interaction of the glycopolymers with HA was estimated as 1.8-2.7. Considering one HA molecule has three sugar-binding pockets, these values were reasonable. The binding mode of synthetic glycopolymer-ligands toward lectins could be tuned using controlled radical polymerization techniques.

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Hoshinoamides A and B, Acyclic Lipopeptides from the Marine Cyanobacterium Caldora penicillata

Iwasaki A., Tadenuma T., Sumimoto S., Shiota I., Matsubara T., Saito-Nakano Y., Nozaki T., Sato T., Suenaga K.

Journal of Natural Products （Journal of Natural Products）  81 （ 11 ） 2545 - 2552 2018年11月

ISSN  01633864

　概要を見る

Hoshinoamides A (1) and B (2), new acyclic lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata. Their structures were elucidated by spectroscopic analyses and degradation reactions. Hoshinoamides A (1) and B (2) did not exhibit any cytotoxicity against HeLa cells at 10 μM, but inhibited the in vitro growth of the malarial parasite Plasmodium falciparum (IC50 = 0.52 and 1.0 μM, respectively).

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Amyloid- fibrils assembled on ganglioside-enriched membranes contain both parallel -sheets and turns

Matsubara T., Yasumori H., Ito K., Shimoaka T., Hasegawa T., Sato T.

Journal of Biological Chemistry （Journal of Biological Chemistry）  293 （ 36 ） 14146 - 14154 2018年09月

ISSN  00219258

　概要を見る

Some protein and peptide aggregates, such as those of amyloid- protein (A), are neurotoxic and have been implicated in several neurodegenerative diseases. A accumulates at nanoclusters enriched in neuronal lipids called gangliosides in the presynaptic neuronal membrane, and the resulting oligomeric and/or fibrous forms accelerate the development of Alzheimer’s disease. Although the presence of A deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between A secondary structure and topography are still unclear. Here, we first confirmed by atomic force microscopy that A40 fibrils can be obtained by incubating seed-free A40 monomers with a membrane composed of sphingomyelin, cholesterol, and the ganglioside GM1. Using Fourier transform infrared (FTIR) reflection–absorption spectroscopy, we then found that these lipid-associated fibrils contained parallel -sheets, whereas self-assembled A40 molecules formed antiparallel -sheets. We also found that the fibrils obtained at GM1-rich nanoclusters were generated from turn A40. Our findings indicate that A generally self-assembles into antiparallel -structures but can also form protofibrils with parallel -sheets by interacting with ganglioside-bound A. We concluded that by promoting the formation of parallel -sheets, highly ganglioside-enriched nanoclusters help accelerate the elongation of A fibrils. These results advance our understanding of ganglioside-induced A fibril formation in neuronal membranes and may help inform the development of additional therapies for Alzheimer’s disease.

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Izenamides A and B, Statine-Containing Depsipeptides, and an Analogue from a Marine Cyanobacterium

Kanamori Y., Iwasaki A., Sumimoto S., Matsubara T., Sato T., Suenaga K.

Journal of Natural Products （Journal of Natural Products）  81 （ 7 ） 1673 - 1681 2018年07月

ISSN  01633864

　概要を見る

Izenamides A, B, and C (1-3), new linear depsipeptides, were isolated from a taxonomically distinct marine cyanobacterium. Izenamides A and B contain a statine moiety [(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid] and inhibited the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10 μM.

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Responsibility of lipid compositions for the amyloid ß assembly induced by ganglioside nanoclusters in mouse synaptosomal membranes

Matsubara T., Kojima T., Fukuda R., Iijma K., Hirai M., Yamamoto N., Yanagisawa K., Sato T.

Polymer Journal （Polymer Journal）  50 （ 8 ） 745 - 752 2018年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00323896

　概要を見る

The assembly of amyloid ß protein (Aß) on ganglioside-enriched microdomains in presynaptic neuronal membranes is involved in the onset of Alzheimer’s disease. We previously found that a highly enriched ganglioside domain generated in a reconstituted lipid bilayer composed of synaptosomal lipids functioned as an Aß-sensitive ganglioside nanocluster (ASIGN) that may induce a spherical Aß assembly. In the present study, the major lipid components of a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from an aged mouse brain were identified, and we demonstrate that the proportion of Aß-insensitive gangliosides such as GM3 directly affects the Aß assembly in synaptosomal membranes. Liquid chromatography coupled to mass spectrometry analyses indicated that ganglio a-series gangliosides (GM1, GM2, GM3, and GD1a) were abundant in DRM fractions. In addition, the GM3/GM1 ratio and the cholesterol content in the synaptosomal fraction differed from those in the non-synaptosomal fraction, in which GM1 and GM3 are sensitive and insensitive gangliosides, respectively. The highly enriched ganglioside nanocluster was identified by the surface topography of ternary mixed lipid bilayers composed of gangliosides, sphingomyelin, and cholesterol. Our results indicate that the composition of gangliosides is responsible for the characteristics of the nanocluster generated in the presynaptic neuronal membranes.

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Novel hemagglutinin-binding sulfated oligofucosides and their effect on influenza virus infection

Kosono S., Kasai A., Komaba S., Matsubara T., Sato T., Takahashi D., Toshima K.

Chemical Communications （Chemical Communications）  54 （ 54 ） 7467 - 7470 2018年

ISSN  13597345

　概要を見る

Among a series of chemically synthesized fucoidan derivatives (1-9), 5 was found for the first time to bind to influenza virus hemagglutinins (HAs) and inhibit hemagglutination activity. In addition, a designed C3-symmetric tripodal ligand 10, synthesized with three sulfated oligofucoside moieties of 5, exhibited much greater hemagglutination inhibition activity than 5. A plaque assay using MDCK cells demonstrated that 10 effectively inhibited influenza virus infection.

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Size and shape of amyloid fibrils induced by ganglioside nanoclusters: role of sialyl oligosaccharide in fibril formation

Teruhiko Matsubara, Masaya Nishihara, Hanaki Yasumori, Mako Nakai, Katsuhiko Yanagisawa, Toshinori Sato

Langmuir 33 （ 48 ） 13874 - 13881 2017年11月

研究論文（学術雑誌）, 共著, 査読有り

• Access to Document (DOI)

Design of glycopolymers carrying sialyl oligosaccharides for controlling the interaction with the influenza virus

Masanori Nagao, Yurina Fujiwara, Teruhiko Matsubara, Yu Hoshino, Toshinori Sato, Yoshiko Miura

Biomacromolecules 18 （ 12 ） 4385 - 4392 2017年11月

研究論文（学術雑誌）, 共著, 査読有り

• Access to Document (DOI)

Kohamamides A, B and C, Cyclic Depsipeptides from an Okeania sp. Marine Cyanobacterium

Arihiro Iwasaki, Ikuma Shiota, Shinpei Sumimoto, Teruhiko Matsubara, Toshinori Sato, Kiyotake Suenaga

J. Nat. Prod. 80 （ 6 ） 1948 - 1952 2017年05月

研究論文（学術雑誌）, 共著, 査読有り

• Access to Document (DOI)

Selective Intracellular Delivery of Ganglioside GM3-Binding Peptide through Caveolae/Raft-Mediated Endocytosis

Teruhiko Matsubara, Ryohei Otani, Miki Yamashita, Haruka Maeno, Hanae Nodono, and Toshinori Sato

Biomacromolecules 18 （ 2 ） 355 - 362 2017年01月

研究論文（学術雑誌）, 共著, 査読有り

• Access to Document (DOI)

Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide.

Teruhiko Matsubara, Michiko Ujie, Takashi Yamamoto, Miku Akahori, Yasuaki Einaga, Toshinori Sato

Proc. Natl. Acad. Sci. U.S.A. 113 （ 32 ） 8981 - 8984 2016年07月

研究論文（学術雑誌）, 共著, 査読有り

• Access to Document (DOI)

Binding of hemagglutinin and influenza virus to a peptide-conjugated lipid membrane

Teruhiko Matsubara, Rabi Shibata, and Toshinori Sato

Front. Microbiol. 7 （ 468 ） 1 - 9 2016年04月

研究論文（学術雑誌）, 共著, 査読有り

Heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy

Teruhiko Matsubara, Ai Onishi, Daisuke Yamaguchi, Toshinori Sato

Bioorg. Med. Chem. 24 （ 5 ） 1106 - 1114 2016年03月

研究論文（学術雑誌）, 共著, 査読有り

体液類似環境におけるアパタイト結合性ペプチド樹状オリゴマーによるミネラリゼーション

橋詰　峰雄, 小野上　綾乃, 飯島　一智, 松原　輝彦, 内田　祐樹, 佐藤　智典

高分子論文集 73 （ 1 ） 55 - 61 2016年01月

研究論文（学術雑誌）, 共著, 査読有り

糖鎖模倣ペプチドのインフルエンザヘマグルチニンに対する結合活性の多価効果

松原 輝彦, 大西 愛, 齋藤 智美, 山口 大介, 佐藤 智典

高分子論文集 73 （ 1 ） 62 - 68 2016年01月

研究論文（学術雑誌）, 共著, 査読有り

Mebamamides A and B, Cyclic Lipopeptides Isolated from the Green Alga Derbesia marina

Arihiro Iwasaki, Osamu Ohno, Shinpei Sumimoto, Teruhiko Matsubara, Satoshi Shimada, Toshinori Sato, Kiyotake Suenaga

J. Nat. Prod. 78 （ 4 ） 901 - 908 2015年04月

研究論文（学術雑誌）, 共著, 査読有り

Imbalance in fatty-acid-chain length of gangliosides triggers Alzheimer amyloid deposition in the precuneus

松原 輝彦

PLoS One 10 （ 3 ） e0121356 2015年03月

研究論文（学術雑誌）, 共著, 査読有り

Synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally-functionalized with hemagglutinin-binding peptide

松原 輝彦

J. Med. Chem. 57 （ 20 ） 8332 - 8339 2014年10月

研究論文（学術雑誌）, 共著, 査読有り

細胞表面のオリゴ糖鎖の謎を解く分子を創る

松原 輝彦

化学と教育 61 （ 5 ） 234 - 235 2013年05月

研究論文（学術雑誌）, 単著

Density of GM1 in Nanoclusters Is a Critical Factor in the Formation of a Spherical Assembly of Amyloid β-Protein on Synaptic Plasma Membranes

Teruhiko Matsubara, Kazutoshi Iijima, Naoki Yamamoto, Katsuhiko Yanagisawa, and Toshinori Sato

Langmuir 29 （ 7 ） 2258-2264 2013年

研究論文（学術雑誌）, 共著, 査読有り

Incorporation of glycosylated amino acid into protein by an in vitro translation system

松原 輝彦

Bioorg. Med. Chem. Lett. 23 （ 20 ） 5634 - 5636 2013年

研究論文（学術雑誌）, 共著, 査読有り

Potential of peptides as inhibitors and mimotopes: selection of carbohydrate-mimetic peptides from phage display libraries

松原 輝彦

J. Nucleic Acids 740982   1-15 2012年

研究論文（学術雑誌）, 単著, 査読有り

Brain insulin resistance accelerates Aß fibrillogenesis by inducing GM1 ganglioside clustering in the presynaptic membranes

Yamamoto N, Matsubara T, Sobue K, Tanida M, Kasahara R, Naruse K, Taniura H, Sato T, Suzuki K.

J. Neurochem. 121 （ 4 ） 619-628 2012年

研究論文（学術雑誌）, 共著, 査読有り

Carbohydrate recognition by pentadecapeptide ligands for a series of sialylated oligosaccharides

松原 輝彦

Bioorg. Med. Chem. 20 （ 21 ） 6452-6458 2012年

研究論文（学術雑誌）, 共著, 査読有り

Calcium Phosphate Mineralization Induced by Synthetic Peptides Having Different Distributions in Simulated Body Fluids

松原 輝彦

Chem. Lett. 41   588-590 2012年

研究論文（学術雑誌）, 共著, 査読有り

パンデミックH1N1/2009：耐性ウイルスの蔓延は防げるか

松原 輝彦

ファルマシア 47 （ 5 ） 445-446 2011年05月

研究論文（学術雑誌）, 単著

ライブラリー選択法による糖鎖認識を制御する新規ペプチドの開発

松原 輝彦・佐藤 智典

バイオインダストリー （シーエムシー出版）  27 （ 2 ） 49 - 53 2010年02月

研究論文（学術雑誌）, 共著

Acrosome reaction-related steroidal saponin, Co-ARIS, from the starfish induces structural changes in microdomains

Masahiro Naruse, Hiroyuki Suetomo, Teruhiko Matsubara, Toshinori Sato, Hiroshi Yanagawa, Motonori Hoshi, and Midori Matsumoto

Dev. Biol. 347   147-153 2010年

研究論文（学術雑誌）, 共著, 査読有り

Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy

Teruhiko Matsubara, Ai Onishi, Tomomi Saito, Aki Shimada, Hiroki Inoue, Takao Taki, Kyosuke Nagata, Yoshio Okahata, and Toshinori Sato

J. Med. Chem. 53 （ 11 ） 4441-4449 2010年

研究論文（学術雑誌）, 共著, 査読有り

ライブラリー選択法による生体分子のデザイン：糖鎖の相互作用を制御するペプチド

松原 輝彦

化学と工業 （日本化学会）  62 （ 10 ） 1091-1093 2009年10月

研究論文（学術雑誌）, 単著, 査読有り

デザインされたペプチドによる細胞膜内スフィンゴ糖脂質ナノドメインの特異的検出

松原 輝彦

生命化学研究レター （生命化学研究会）  29   21-27 2009年02月

研究論文（学術雑誌）, 単著, 査読有り

最新のトピックス、高病原性の新型インフルエンザウイルスはどのように発生するか？

松原 輝彦・佐藤智典

月刊「化学」 （化学同人）  64 （ 1 ） 74-75 2009年01月

研究論文（学術雑誌）, 共著

Observations of the distribution of GM3 in membrane microdomains by atomic force microscopy

Kazutoshi Iijima, Norihiro Soga, Teruhiko Matsubara, Toshinori Sato

J. Colloid Interface Sci. 337   369-374 2009年

研究論文（学術雑誌）, 共著, 査読有り

Inhibition of Influenza Virus Infections by Sialylgalactose-Binding Peptides Selected from a Phage Library

Teruhiko Matsubara, Machiko Sumi, Hiroyuki Kubota, Takao Taki, Yoshio Okahata, and Toshinori Sato

J. Med. Chem. 52 （ 14 ） 4247-4256 2009年

研究論文（学術雑誌）, 共著, 査読有り

Protease-catalyzed dipeptide synthesis from N-protected amino acid carbamoylmethyl esters and free amino acids in frozen aqueous solutions

Sayed Mohiuddin Abdus Salam, Ken-ichi Kagawa, Teruhiko Matsubara, Katsuhiro Kawashiro

Enzyme Microb. Technol. 43   537-543 2008年

研究論文（学術雑誌）, 単著, 査読有り

Selection of carbohydrate-binding domain with a helix-loop helix structure

Teruhiko Matsubara, Mie Iida, Takeshi Tsumuraya, Ikuo Fujii, and Toshinori Sato

Biochemistry 47 （ 26 ） 6745-6751 2008年

研究論文（学術雑誌）, 共著, 査読有り

Lipase-catalyzed enantioselective hydrolysis of N-protected racemic non-protein amino acid esters

Ken-ichi Kagawa, Teruhiko Matsubara, and Katsuhiro Kawashiro

Biocatal. Biotrans. 26 （ 3 ） 186-196 2008年

研究論文（学術雑誌）, 共著, 査読有り

Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid beta-protein fibrillogenesis

Naoki Yamamoto, Teruhiko Matsubara, Toshinori Sato, and Katsuhiko Yanagisawa

Biochim. Biophys. Acta 1778   2717-2726 2008年

研究論文（学術雑誌）, 共著, 査読有り

Specific binding of GM1-binding peptides to high-density GM1 in lipid membranes

Teruhiko Matsubara, Kazutoshi Iijima, Miwa Nakamura, Takao Taki, Yoshio Okahata, and Toshinori Sato

Langmuir 23 （ 2 ） 708-714 2007年

研究論文（学術雑誌）, 共著, 査読有り

A simple two-transition model for loss of infectivity of phages on exposure to organic solvent

Teruhiko Matsubara, Wakako Emoto and Katsuhiro Kawashiro

Biomol. Eng. 24 （ 2 ） 269–271 2007年

研究論文（学術雑誌）, 共著, 査読有り

Structural Transition Study of a Fifteen Amino Acid Residue Peptide Induced by GM1

N. Fujitani, H. Shimizu, T. Matsubara, T. Ohta, Y. Komata, N. Muira, T. Sato, and S.-I. Nishimura

Carbohydr. Res. 2007年

研究論文（学術雑誌）, 共著, 査読有り

Identification of oligosaccharide-recognition molecules by phage-display technology

T. Matsubara and T. Sato

Trends Glycosci. Glycotechnol. 19 （ 107 ） 133-145 2007年

研究論文（学術雑誌）, 共著, 査読有り

Selective Precipitation of Salts on the Surface of a Gel State Phosphatidylcholine Membrane

Kazutoshi Iijima, Teruhiko Matsubara, Toshinori Sato

Chem. Lett. 2007年

研究論文（学術雑誌）, 共著, 査読有り

糖鎖の「ふり」をしてウイルスを騙すペプチド

松原輝彦

生体機能関連化学部会ニュースレター （日本化学会生体機能関連化学部会）  21 （ 3 ） 21-25 2006年

研究論文（その他学術会議資料等）, 共著

展開単分子膜を利用したオリゴ糖鎖結合性ペプチドの分子設計戦略

松原輝彦・佐藤智典

高分子加工 （高分子学会）  54 （ 6 ） 266-269 2005年06月

研究論文（学術雑誌）, 単著, 査読有り

Stability of Protease in Organic Solvent: Structural Identification by Solid-State NMR of Lyophilized Papain Before and After 1-Propanol Treatment and the Corresponding Enzymatic Activities

Teruhiko Matsubara, Risa Fujita, Shigeru Sugiyama, and Katsuhiko Kawashiro

Biotech. Bioeng. 93 （ 5 ） 928-933 2005年

研究論文（学術雑誌）, 共著

A Peptide Motif Recognizing a Polymer Stereoregularity

Takeshi Serizawa, Toshiki Sawada, Hisao Matsuno, Teruhiko Matsubara, and Toshinori Sato

J. Am. Chem. Soc. 127 （ 40 ） 13780-13781 2005年

研究論文（学術雑誌）, 共著, 査読有り

ランダムライブラリーからの選択手法：糖鎖関連タンパク質の創製に向けて

松原 輝彦

生命化学研究レター （生命化学研究会）  14   7-10 2004年02月

研究論文（学術雑誌）, 単著, 査読有り

酵素分子を変異ライブラリーから選択する方法論の開発

松原 輝彦

化学と工業 56 （ 4 ） 487 2003年04月

研究論文（学術雑誌）, 単著, 査読有り

Selection of novel structural zinc sites from a random peptide library

Teruhiko Matsubara, Yuko Hiura, Osamu Kawahito, Mikito Yasuzawa, Katsuhiro Kawashiro

FEBS Letters 555 （ 2 ） 317-321 2003年

研究論文（学術雑誌）, 共著, 査読有り

Biocombinatorial Selection of Metal Ion-Chelating Peptides

T. Matsubara, Y. Hiura, K. Kawashiro

Int. J. Modern Phys. B 17 （ 8-9 ） 1324-1328 2003年

研究論文（研究会，シンポジウム資料等）, 共著, 査読有り

ガングリオシド単分子膜を用いた糖鎖認識ペプチドのセレクション技術

松原 輝彦

徳島大学工学部研究報告 46   3 2001年

研究論文（大学，研究機関等紀要）, 単著, 査読有り

Ganglioside-binding Peptides selected from a Combinatorial Library and Their Carbohydrate Recognition

松原 輝彦

Trends in Glycoscience and Glycotechnology 13 （ 73 ） 557-560 2001年

研究論文（学術雑誌）, 単著

Selection of ganglioside GM1-binding peptides by using a phage library

T. Matsubara, D. Ishikawa, T. Taki, Y. Okahata, T. Sato

FEBS Letters 456   253-256 1999年

研究論文（学術雑誌）, 共著, 査読有り

Electrochemical Properties of Poly(L-2-anthraquinonylalanine)

H. Shinohara, T. Matsubara, M. Sisido

Macromolecules 30 （ 9 ） 2657-2661 1997年

研究論文（学術雑誌）, 共著, 査読有り

Design and Synthesis of Peptides and Polypeptides of Electron Transporting Functions

M. Sisido, T. Matsubara, and H. Shinohara

Peptide Chemistry 1996   473-476 1997年

研究論文（研究会，シンポジウム資料等）, 共著, 査読有り

Synthesis and Redox Property of Polypeptides Containing L-Ferrocenylalanine

M. Kira, T. Matsubara, H. Shinohara, M. Sisido

Chemistry Letters 1997 （ 1 ） 89-90 1997年

研究論文（学術雑誌）, 共著, 査読有り

Synthesis and Conformation of Poly(L-2-anthraquinonylalanine)

T. Matsubara, M. Sisido

Macromolecules 30 （ 9 ） 2651-2656 1997年

研究論文（学術雑誌）, 共著, 査読有り