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Multinuclear Dynamic NMR of Diffusion and Transport of Popypeptides by Membrane Thermal Fluctuation

Research Project

Project/Area Number 24550035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical chemistry
Research InstitutionHimeji Dokkyo University

Principal Investigator

Okamura Emiko  姫路獨協大学, 薬学部, 教授 (00160705)

Co-Investigator(Kenkyū-buntansha) AKI KENZO  姫路獨協大学, 薬学部, 助手 (50714945)
TAKECHI YUKI (HARAYA YUKI)  姫路獨協大学, 薬学部, 助教 (30634604)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords生物物理 / 界面・表面物性 / 超精密解析 / NMR / 膜輸送 / 膜透過
Outline of Final Research Achievements

Molecular dynamics in membrane inside and outside was quantified by multinuclear, dynamic NMR in situ, in relation to the thermal fluctuation of membranes. First, the lipid membrane dynamics was successfully characterized in cell sized vesicles (CSVs) of 10-20 μm-diameters by using solution-state NMR. The dynamic structure of CSVs was found to be different from nano-sized vesicles of ~100 nm-diameters frequently used. The contribution of membrane fluctuation to molecular transport was also quantified in the presence of various amounts of cholesterol in the membrane.
The peptide permeation to living cell inside was also observed by real-time in-cell NMR in situ and analyzed by first-order kinetics. Such kinetic approach was also applicable to time-resolved studies of biochemical reactions in peptides such as peptide bond cleavage in human-lens crystallin fragment in situ.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (47 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 5 results) Presentation (33 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (1 results) Remarks (4 results)

  • [Journal Article] D-β-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage2016

    • Author(s)
      Kenzo Aki and Emiko Okamura
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 21594-21594

    • DOI

      10.1038/srep21594

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Kinetics of Membrane Binding and Mobility of Drugs by Multinuclear Dynamic NMR <i>in Situ</i>2016

    • Author(s)
      Emiko Okamura
    • Journal Title

      Journal of The Society of Japanese Women Scientists

      Volume: 16 Issue: 1 Pages: 7-14

    • DOI

      10.5939/sjws.16002

    • NAID

      130005142362

    • ISSN
      1349-4449, 2186-3776
    • Related Report
      2015 Annual Research Report
    • Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of Phospholipid Protrusion in the Cell Sized Vesicle by Hydrophobic Bisphenol A2015

    • Author(s)
      Y. Takechi, Y. Shintani, D. Kimoto, and E. Okamura
    • Journal Title

      Membrane

      Volume: 40 Pages: 38-45

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Staggered side-chain conformers of aspartyl residues prerequisite to transformation from L-α- to D-β-aspartate 58 in human-lens αA-crystallin fragment2015

    • Author(s)
      K. Aki and E. Okamura
    • Journal Title

      Biophysical Chemistry

      Volume: 196 Pages: 10-15

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Uptake of Sevoflurane Limited by the Presence of Cholesterol in the Lipid Bilayer Membrane: A Multinuclear Nuclear Magnetic Resonance Study2014

    • Author(s)
      E. Okamura, Y. Takechi, and K. Aki
    • Journal Title

      Journal of Oleo Science

      Volume: 63 Issue: 11 Pages: 1149-1157

    • DOI

      10.5650/jos.ess14120

    • NAID

      130004693947

    • ISSN
      1345-8957, 1347-3352
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 柔らかな生体界面の構造と機能:膜の動きと物質輸送のNMR2014

    • Author(s)
      岡村恵美子
    • Journal Title

      Colloid & Interface Communication

      Volume: 39 Pages: 23-25

    • NAID

      40020459624

    • Related Report
      2014 Research-status Report
  • [Journal Article] Lateral diffusion of lipids separated from rotational and translational diffusion of a fluid large unilamellar vesicle2013

    • Author(s)
      Noriyuki Yoshii, Tomomi Emoto, Emiko Okamura
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 106 Pages: 22-27

    • DOI

      10.1016/j.colsurfb.2013.01.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Slow Tumbling but Large Protrusion of Phospholipids in the Cell Sized Giant Vesicle.2013

    • Author(s)
      Takechi, Y., Saito, H., and Okamura, E
    • Journal Title

      Chem. Phys. Lett

      Volume: 570 Pages: 136-140

    • DOI

      10.1016/j.cplett.2013.03.048

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Physicochemical Mechanism for the Lipid Membrane Binding of Polyarginine: the Favorable Enthalpy Change with Structural Transition from Random Coil to α-Helix2012

    • Author(s)
      Takechi, Y., Mizuguchi, C., Tanaka, M., Kawakami, T., Aimoto, S., Okamura, E., and Saito, H
    • Journal Title

      Chem. Lett

      Volume: 41(10) Issue: 10 Pages: 1374-1376

    • DOI

      10.1246/cl.2012.1374

    • NAID

      10031120691

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] アスパラギン酸異性体の異性化とペプチド鎖分解の速度論解析2016

    • Author(s)
      安岐健三, 岡村恵美子
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学 京田辺キャンパス(京都)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mobility, location, and kinetics of membrane binding and delivery of drugs by solution-state 19F and 1H NMR2015

    • Author(s)
      Emiko Okamura
    • Organizer
      6th Asian Conference on Colloid and Interface Science
    • Place of Presentation
      Arkas Sasebo, Nagasaki, Japan
    • Year and Date
      2015-11-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] L-α-およびD-β-アスパラギン酸含有ペプチドの分解と異性化反応の速度論:リアルタイムNMRとHPLCによる解析2015

    • Author(s)
      安岐健三, 岡村恵美子
    • Organizer
      第8回「タンパク質の異常凝集とその防御・修復機構に関する研究会」
    • Place of Presentation
      京都大学原子炉実験所(大阪)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] リアルタイムNMR測定によるL-α-およびD-β-アスパラギン酸異性体含有ペプチドの分解速度の解析2015

    • Author(s)
      安岐健三, 岡村恵美子
    • Organizer
      第38回溶液化学シンポジウム
    • Place of Presentation
      高知市文化プラザ かるポート(高知)
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 水晶体タンパク質模擬ペプチド中のAsp異性化に関わる側鎖の立体配座のNMR研究2015

    • Author(s)
      岡村恵美子
    • Organizer
      第15回日本蛋白質科学会年会ワークショップ「蛋白質とアミノ酸のキラルサイエンス」
    • Place of Presentation
      あわぎんホール(徳島)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] キネティクスに基づく細胞へのオクタアルギニンの物理的膜透過メカニズム2015

    • Author(s)
      武知(原矢)佑樹, 安岐健三, 通山由美, 原野雄一, 川上徹, 斎藤博幸, 岡村恵美子
    • Organizer
      日本膜学会第37年会
    • Place of Presentation
      早稲田大学 西早稲田キャンパス(東京)
    • Year and Date
      2015-05-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] アスパラギン酸の異性化に関わる側鎖の立体配座 :αAクリスタリン模擬ペプチドの高分解能1H-NMR解析2015

    • Author(s)
      安岐健三、岡村恵美子
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] アスパラギン酸の異性化に関わる側鎖の立体配座の高分解能1H-NMR解析:αAクリスタリン模擬ペプチドを例として2014

    • Author(s)
      岡村恵美子
    • Organizer
      第7回「タンパク質の異常凝集とその防御・修復機構に関する研究会」
    • Place of Presentation
      京都大学原子炉実験所(大阪)
    • Year and Date
      2014-12-11 – 2014-12-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] コレステロールによる麻酔剤セボフレンの取り込み制御に関する動的多核NMR研究2014

    • Author(s)
      岡村恵美子、武知佑樹、安岐健三
    • Organizer
      膜シンポジウム2014
    • Place of Presentation
      神戸大学百年記念館(神戸)
    • Year and Date
      2014-11-26 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 水晶体タンパク質模擬ペプチド中のAsp異性化におよぼすAsp側鎖の立体配座の高分解能1H-NMRによる解析2014

    • Author(s)
      安岐健三、岡村恵美子
    • Organizer
      第37回溶液化学シンポジウム
    • Place of Presentation
      アバンセ(佐賀)
    • Year and Date
      2014-11-12 – 2014-11-14
    • Related Report
      2014 Research-status Report
  • [Presentation] αAクリスタリン模擬ペプチドにおけるα→β Asp異性化におよぼすAsp側鎖の立体配座の高分解能1H-NMR解析2014

    • Author(s)
      安岐健三、岡村恵美子
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都薬科大学(京都)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] In cell NMRによるオクタアルギニンペプチドの細胞内輸送のリアルタイム計測と速度論2014

    • Author(s)
      武知佑樹、安岐健三、通山由美、川上徹、斎藤博幸、岡村恵美子
    • Organizer
      第65回コロイドおよび界面化学討論会
    • Place of Presentation
      東京理科大学(東京)
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 Research-status Report
  • [Presentation] Real Time in-Cell 19F NMR Spectroscopy on the Cell Membrane Permeation of Octaarginine2014

    • Author(s)
      Y. Takechi, K. Aki, Y. Tohyama, T. Kawakami, H. Saito, and E. Okamura
    • Organizer
      XXVIth International Conference on Magnetic Resonance in Biological Systems
    • Place of Presentation
      Hyatt Regency Hotel, Dallas, Texas, USA
    • Year and Date
      2014-08-24 – 2014-08-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 疎水性物質による細胞サイズベシクル膜中リン脂質の突出運動の制御2014

    • Author(s)
      岡村恵美子
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス(名古屋)
    • Related Report
      2013 Research-status Report
  • [Presentation] Delivery of Sevoflurane Limited by the Presence of Cholesterol in Lipid Bilayer Membranes: Multinuclear, Dynamic NMR in Situ2014

    • Author(s)
      E. Okamura
    • Organizer
      Joint Meeting of JOCS-AOCS in 2014 (in 105th AOCS Annual Meeting & Expo)
    • Place of Presentation
      Henry B. Gonzalez Convention Center, San Antonio, Texas, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] オクタアルギニンの物理的膜透過に関するリアルタイムin cell NMR研究2014

    • Author(s)
      武知佑樹
    • Organizer
      日本膜学会第36年会
    • Place of Presentation
      早稲田大学西早稲田キャンパス(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] 溶液NMRによるリポソーム膜の動的構造と薬物輸送研究への展開2014

    • Author(s)
      岡村恵美子
    • Organizer
      第32回物性物理化学研究会
    • Place of Presentation
      京都大学薬学部記念講堂(京都)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Motions and Fluctuations of Phospholipid Molecules in Large and Cell Sized Vesicles by NMR2013

    • Author(s)
      E. Okamura
    • Organizer
      33rd International Conference on Solution Chemistry
    • Place of Presentation
      Kyoto Terrsa, Kyoto, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] αAクリスタリンの部分ペプチドを用いたAsp異性化シミュレーション2013

    • Author(s)
      安岐健三
    • Organizer
      第86回日本生化学大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 疎水性物質による細胞サイズベシクル膜の揺らぎの抑制2013

    • Author(s)
      武知佑樹
    • Organizer
      膜シンポジウム2013
    • Place of Presentation
      京都府立医科大学(京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞サイズベシクル膜の揺らぎにあたえる疎水性物質やイオンの影響2013

    • Author(s)
      武知佑樹
    • Organizer
      第35回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      東京大学本郷キャンパス(東京)
    • Related Report
      2013 Research-status Report
  • [Presentation] NMR核オーバーハウザー効果から見た細胞サイズベシクル中におけるリン脂質分子のダイナミクス2013

    • Author(s)
      武知 佑樹
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      立命館大学びわこくさつキャンパス(滋賀)
    • Related Report
      2012 Research-status Report
  • [Presentation] 曲率の小さな細胞モデル膜中のリン脂質分子のダイナミクス2013

    • Author(s)
      武知 佑樹
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      早稲田大学西早稲田キャンパス(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 分子動力学シミュレーションによる生体膜中の薬物の結合構造2012

    • Author(s)
      吉井 範行
    • Organizer
      日本膜学会第34年会
    • Place of Presentation
      早稲田大学西早稲田キャンパス(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Physicochemical Mechanism for the Enhanced Ability of Lipid Membrane Penetration of Polyarginine2012

    • Author(s)
      Yuki Takechi
    • Organizer
      14th International Association of Colloid and Interface Scientists Conference
    • Place of Presentation
      Sendai International Center, Sendai, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Kinetics of Membrane Binding and Mobility of Drugs by Multinuclear Dynamic NMR in Situ2012

    • Author(s)
      Emiko Okamura
    • Organizer
      14th International Association of Colloid and Interface Scientists Conference
    • Place of Presentation
      Sendai International Center, Sendai, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞サイズリポソーム中の脂質分子の揺らぎ2012

    • Author(s)
      岡村 恵美子
    • Organizer
      新学術領域研究「揺らぎと生体機能」・「水を主役としたATPエネルギー変換」合同公開シンポジウム「ゆらぎと水-生命のエネルギーと機能の分子機構を探る」
    • Place of Presentation
      大阪ガーデンパレス(大阪)
    • Related Report
      2012 Research-status Report
  • [Presentation] Static and Dynamic Behaviors of Drug Delivery to Lipid Bilayer Membrane by NMR and Molecular Dynamics Simulation2012

    • Author(s)
      Emiko Okamura
    • Organizer
      World Congress on Oleo Science & 29th ISF Congress
    • Place of Presentation
      Arkas Sasebo, Nagasaki, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] カチオン性ポリペプチドと酸性脂質膜の相互作用解析―ポリペプチド-膜間相互作用に与えるアルギニンとリジンの影響―2012

    • Author(s)
      武知 佑樹
    • Organizer
      第62回日本薬学会近畿支部大会
    • Place of Presentation
      武庫川女子大学(西宮)
    • Related Report
      2012 Research-status Report
  • [Presentation] 溶液NMRを用いた細胞サイズベシクルの評価2012

    • Author(s)
      武知 佑樹
    • Organizer
      膜シンポジウム2012
    • Place of Presentation
      神戸大学百年記念館(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞サイズベシクルの構造と動態に関する溶液NMR研究2012

    • Author(s)
      武知 佑樹
    • Organizer
      第35回溶液化学シンポジウム
    • Place of Presentation
      早稲田大学西早稲田キャンパス(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞サイズベシクルの高濃度調製と溶液NMRによる物性解析2012

    • Author(s)
      武知 佑樹
    • Organizer
      第34回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      京都大学薬学部記念講堂(京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular Fluctuation of Lipids in Cell Sized Vesicles as Studied by NMR2012

    • Author(s)
      Yuki Takechi
    • Organizer
      The 6th International Symposium on Molecular Science of Fluctuations toward Biological Functions
    • Place of Presentation
      Kyoto Terrsa, Kyoto, Japan
    • Related Report
      2012 Research-status Report
  • [Book] 揺らぎ・ダイナミクスと生体機能(寺嶋正秀編)2013

    • Author(s)
      岡村恵美子
    • Total Pages
      368
    • Publisher
      化学同人
    • Related Report
      2013 Research-status Report
  • [Remarks] 姫路獨協大学薬学部 生物物理化学研究室 研究内容

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/ph/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 姫路獨協大学薬学部 生物物理化学研究室 研究内容

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/ph/bpc-top.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 姫路獨協大学薬学部 生物物理化学研究室 研究内容

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/ph/bpc-top.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 姫路獨協大学薬学部 生物物理化学研究室 研究内容

    • URL

      http://www.himeji-du.ac.jp/faculty/dp_pharm/pharm/ph/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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