KEIO RESEARCHERS INFORMATION SYSTEM

Profile Summary 【 Display / hide 】

Profile Summary 【 Display / hide 】

• Design of peptide-based bionanomolecules for specific probes and inhibitors against oligosaccharide-related diseases including virus infection. Development of a new generation of chemical biology using contactless drops generated by acoustic levitation toward containerless processing.

Career 【 Display / hide 】

Career 【 Display / hide 】

• 1999.01

  -

  2000.06

  日本学術振興会　特別研究員

• 2000.07

  -

  2003.03

  徳島大学工学部　助手

• 2003.04

  -

  2007.03

  大学助手(理工学部生命情報学科)

• 2007.04

  -

  2008.03

  大学助教(職位変更による)(理工学部生命情報学科)

• 2008.04

  -

  2019.03

  大学専任講師(理工学部生命情報学科)

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1995.03

  Okayama University, 工学部, 生体機能応用工学科

  University, Graduated

• 1997.03

  Okayama University, Graduate School, Division of Engineering, 生体機能応用工学専攻

  Graduate School, Completed, Master's course

• 2000.03

  Tokyo Institute of Technology, Graduate School, Division of Life Science and Engineering, バイオテクノロジー専攻

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• Ph.D., Tokyo Institute of Technology, Coursework, 2000.03

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Bio chemistry (Chemistry Related to Living Body)

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• ganglioside

• phage display

• peptide library

• glycoconjugate

• 音響浮揚

Proposed Theme of Joint Research 【 Display / hide 】

Proposed Theme of Joint Research 【 Display / hide 】

• オリゴ糖鎖のクラスターに結合する分子の利用

  Interested in joint research with industry (including private organizations, etc.),  Desired form： Technical Consultation, Funded Research, Cooperative Research, Other

• ファージ提示法による標的分子および物質に対するランダムライブラリーからのペプチドおよびタンパク質の選択

  Interested in joint research with other research organizations (including universities, etc.)

Books 【 Display / hide 】

Books 【 Display / hide 】

• Influenza Virus

  Matsubara T., Sato T., Diamond Electrodes Fundamentals and Applications, 2022.01

  　View Summary

  The rapid diagnosis of patients in clinical practice is important for anti-influenza therapy. However, since the sensitivity of conventional rapid diagnostic test kits is low, false-negative results are often produced. Therefore, simple and convenient test kits with high sensitivity are needed in clinical practice. In this chapter, we describe the construction of a boron-doped diamond (BDD) electrode that terminates with a receptor (sialic acid-containing oligosaccharide chain)-mimicking peptide as well as its performance in the electrochemical detection of human and avian influenza viruses (IFVs).

  • Access to Document (DOI)

• ペプチド医薬品のスクリーニング・安定化・製剤化技術

  110名, 技術情報協会, 2017.12

  Scope: 6章1節

• 生体分子化学-基礎から応用まで

  杉本 直己, 内藤 昌信, 橋詰 峰雄, 高橋 俊太郎, 田中 直毅, 建石 寿枝, 遠藤 玉樹, 津本 浩平, 長門石 曉, 松原 輝彦, 上田 実, 朝山 章一郎, 講談社サイエンティフィク, 2017.01

  Scope: 9章（p197-224）

• 超分子サイエンス＆テクノロジー

  松原 輝彦・佐藤智典, NTS, 2009.05

  Scope: 1036-1042

• Contemporary Trends in Bacteriophage Research

  MATSUBARA TERUHIKO, Nova Science Publishers, Inc., 2009.05

  Scope: 407-419

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Papers 【 Display / hide 】

Papers 【 Display / hide 】

• 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 2024.04

  　View Summary

  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.

  • Access to Document (DOI)

• 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 2023.12

  　View Summary

  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.

  • Access to Document (DOI)

• 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 )  2023.11

  ISSN  09476539

  　View Summary

  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.

  • Access to Document (DOI)

• 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 2023.03

  ISSN  00027863

  　View Summary

  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.

  • Access to Document (DOI)

• 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 2022.11

  ISSN  01633864

  　View Summary

  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.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Development of a plastic-free bioreaction system using a non-contact reactor

  Matsubara, Teruhiko

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2023

• Novel chem-bio experimental reactor using a non-contact system without plastics

  Matsubara, Teruhiko

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2022

• Development of biosensors for viral detection capable of responding to various mutations

  Matsubara, Teruhiko

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2021

• Development of innovative bioreactor having omnidirectional contactless interface

  Matsubara, Teruhiko

  科学研究費補助金研究成果報告書 2021

• Development of a novel microbioreactor of droplet using ultrasound device

  Matsubara, Teruhiko

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2018

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• Development of a highly efficient method of gene transfer into cells using acoustic levitation

  2024.06

  -

  2026.03

  挑戦的研究（萌芽）, Principal investigator

• Development of target-oriented modification of peptide resources obtained by phage display method

  2023.04

  -

  2025.03

  学術変革領域研究(A), Principal investigator

• 全方位非接触界面による革新的バイオリアクターの開発

  2020.07

  -

  2022.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Principal investigator

• Inhibition mechanism of modified peptide ligands that mimic complicated sugar receptors

  2015.04

  -

  2018.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 東京糖鎖研究会（GlycoTOKYO）奨励賞

  MATSUBARA TERUHIKO, 2010.11, 東京糖鎖研究会（GlycoTOKYO）, ライブラリーを用いた糖鎖-タンパク質間相互作用を制御するペプチドの設計

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 若い世代の特別講演会（第23回）講演証

  MATSUBARA TERUHIKO, 2009.03, 日本化学会第89春季年会2009, ライブラリー選択法で得られた新規ペプチドによる細胞表面糖鎖の機能制御

  Type of Award： Award from Japanese society, conference, symposium, etc.

• バイオ関連化学合同シンポジウム講演賞

  MATSUBARA TERUHIKO, 2006.09, バイオ関連化学合同シンポジウム（日本化学会生体関連化学部会、バイオテクノロジー部会、生命化学研究会）, ヘマグルチニン糖鎖結合ポケットを認識するペプチド分子設計

  Type of Award： Award from Japanese society, conference, symposium, etc.

• ISBC 2003 Poster Award

  Teruhiko Matsubara, 2003.12, First International Symposium on Biomolecular Chemistry, Functions of carbohydrate-binding peptides selected from phage-displayed peptide library

  Type of Award： Award from Japanese society, conference, symposium, etc.

  　View Description

  First International Symposium on Biomolecular Chemistry (ISBC 2003), December 4, 2003

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• TOPICS IN BIOSCIENCES AND INFORMATICS 1

  2025

• SEMINAR IN BIOSCIENCES AND INFORMATICS

  2025

• INTRODUCTION TO BIOLOGY TODAY

  2025

• INTRODUCTION TO BIOLOGY

  2025

• INDEPENDENT STUDY ON FUNDAMENTAL SCIENCE AND TECHNOLOGY

  2025

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本ペプチド学会, 

  2021.04

  -

  Present

• 日本ソノケミストリー学会, 

  2020.04

  -

  Present

• 日本神経化学会, 

  2017.04

  -

  Present

• 日本糖質学会, 

  2004.10

  -

  Present

• 遺伝子・デリバリー研究会, 

  2003.04

  -

  Present

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Committee Experiences 【 Display / hide 】

Committee Experiences 【 Display / hide 】

• 2011.01

  -

  Present

  ASSOCIATE EDITOR, Trends in Glycoscience and Glycotechnology

• 2011.01

  -

  2017.12

  Financial Secretary, FCCA