Research Themes

• Establishment of methods for elucidation, prediction, and regulation of polymer conformations with using computation and spectroscopy
  Grants-in-Aid for Scientific Research
  01 Apr. 2025 - 31 Mar. 2030
  谷口 透
  Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), Hokkaido University, 25H01282
• 溶媒分子を考慮するVCD・NMR・CD計算法の開発ならびに天然物・生物活性分子の構造解析
  科学研究費助成事業
  01 Apr. 2023 - 31 Mar. 2027
  谷口 透
  分子の構造決定におけるNMR・CD計算は一般的になってきたが、「計算が合わない分子」について深く議論されることはない。本研究では、個々の溶媒分子と解析対象分子の相互作用をMDシミュレーションした後に、QM/MM法でVCDを計算する「QM/MM-MD法」を確立する。また本法をNMR・CD計算にも応用する。また本法をNMR・CD計算にも応用する。次にQM/MM-MD法を用いて、従来法では解析困難な脂質・フッ素化分子・特殊ペプチドの立体配置とコンホメーションの解析法を開発する。
  令和５年度はQM/MM-MD計算について各種条件を試行しつつ、各種分子のVCDスペクトル計算を実施してきた。また、脂質やフッ素化分子を含む各種分子の合成を進めた。
  QM/MM-MD計算条件の検討について、各種有機分子に数種のMD条件を適用して得られた結果の差異を解析するとともに、MDスナップショットに対しても各種計算条件を検討した。別途測定したVCDデータと比較することによって計算条件の探索と最適化を行った。分子によっては計算条件にほとんど左右されることなく実測VCDを良く再現するVCDスペクトルが得られた。その一方で、アルコールを有する一部の低分子については溶媒を考慮することによって劇的なVCD計算精度の向上が見られた。
  各種分子の合成について、フッ素化されたアミノ酸や脂質を数種合成するとともに、重水素化された脂質も数種合成した。これらの分子のいくつかについてはすでに各種分光法による解析を進めている。
  日本学術振興会, 基盤研究(B), 北海道大学, 23K26782
• Development of synthetic method for heteroatom-containing polycyclic compounds using carbenoid insertion reaction
  Grants-in-Aid for Scientific Research
  01 Apr. 2020 - 31 Mar. 2023
  Tomohiro Asakawa
  We have developed a key Rh(II)-catalyzed asymmetric construction method for heterocyclic compounds, as well as a new asymmetric total synthesis of sophoraflavanone H, an antiviral compound isolated from Sophora moorcroftiana, and a new construction method for indoline compounds. In the synthesis of sophoraflavanone H, we also succeeded in synthesizing structural analogs, which are expected to be applied to structure-activity relationship studies. This new construction of the indoline skeleton is expected to be applied to the synthesis of new drugs.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Tokai University, 20K06946
• Development of novel stereochemical analytical technique of biomolecules by the VCD exciton chirality method
  Grants-in-Aid for Scientific Research
  01 Apr. 2019 - 31 Mar. 2023
  Monde Kenji
  In order to verify the applicability of IR functional groups such as alkynes, azides, and nitriles to the VCD exciton chirality method, binaphthyl derivatives with two IR functional groups were synthesized and their measured VCD was verified. The relationship between the VCD signal shape and the positional relationship between two IR functional groups was discussed. To apply the VCD exciton chirality method to biomolecules, acylceramides were selected for total synthesis studies. By repeating the coupling reaction, a C34:1 ultra long chain fatty acid was synthesized. Subsequent coupling reactions with sphingo bases and linolenic acid led to the total synthesis of the acylceramide.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H02836
• Development of structural analysis methods for middle-sized and polar molecules by VCD spectroscopy
  Grants-in-Aid for Scientific Research
  01 Apr. 2018 - 31 Mar. 2022
  Taniguchi Tohru
  Middle-sized natural products (M.W. 500 to 2000) such as oligosaccharides, cyclic peptides, macrolides, and other metabolites are promising drug candidates beyond Lipinski’s rule of 5. Because middle-sized molecules target, for example, protein-protein interactions more efficiently than small molecules do, a large number of such drugs have been approved and under development in recent years. For the exploration of such natural products and their synthetic derivatives, their structural elucidation is one of the major bottlenecks as they possess multiple chiral centers. In this work, we developed new methods for structural analysis of middle-sized molecules by using vibrational circular dichroism (VCD) spectroscopy. Furthermore, this work achieved the first preparation of carbodiimides with one-handed axial chirality.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18H02093
• Development of Structural Analysis Method for Middle-Sized and Polar Molecules by VCD and ROA
  Grants-in-Aid for Scientific Research
  2019 - 2022
  Taniguchi Tohru
  Structural determination of novel molecules has often been a bottleneck of various research. Structures of polar molecules and middle-sized molecules are especially difficult to analyze by conventional techniques. In this work, we used vibrational circular dichroism and Raman optical activity spectoscopies to establish a versatile method to analyze molecular stereochemistry and conformation in a solution-state. We showed that this approach is applicable to various molecules such as sugars and lipids.
  Japan Society for the Promotion of Science, Fund for the Promotion of Joint International Research (Fostering Joint International Research (A)), Hokkaido University, 18KK0394
• Development of Non-Enzymatic Method to Translate D-Nucleic Acid to L-Nucleic Acid
  Grants-in-Aid for Scientific Research
  01 Apr. 2016 - 31 Mar. 2018
  Taniguchi Tohru
  Aiming both at creation of mirror-image life and at development of nucleic acid drugs resistant to nucleases, this work studied toward creation of non-enzymatic reaction to translate D-nucleic acid to L-nucleic acid. During the synthesis of L-nucleotide monomers, we succeeded in developing an efficient glycosidation reaction to connect a sugar and a nucleobase. We also established a new method to elucidate the configuration and conformation of furanoside and nucleoside by using vibrational circular dichroism. L-Nucleotides obtained in this study were submitted to solid-state synthesis, which yielded several oligonucleotides containing L-nucleotides. Oligonucleotides containing L-methylcytidines showed high stability when forming a duplex with D-oligonucleotides.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K14028
• 3D structural analysis of (macro)molecules using VCD in the region above 1900 cm-1
  Grants-in-Aid for Scientific Research
  01 Apr. 2014 - 31 Mar. 2017
  Taniguchi Tohru
  Development of a method to analyze molecular stereostructures provides a detailed understanding of the functions of various molecules such as medicines and enzymes and of the origin of life. This work has established a new convenient method for analyzing molecular stereostructures by using vibrational circular dichroism (VCD) spectroscopy. For example, this work has demonstrated its effectiveness toward the secondary structure of macromolecules such as polyesters. Another example for the use of our VCD method is facile determination of lipid molecules that are suggested to have involved in the development of life. Because VCD spectroscopy provides structural information that can not be obtained by the other available methods, this method should deepen our understandings on molecular stereostructures.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (A), Hokkaido University, 26702034
• Development of the novel determination methodology for absolute configuration without theoretical calculation
  Grants-in-Aid for Scientific Research
  01 Apr. 2012 - 31 Mar. 2015
  MONDE Kenji, TANIGUCHI Tohru, MURAI Yuta
  Vibrational circular dichroism (VCD) is a reliable and non-empirical method which can determine absolute configuration. However, ab initio theoretical calculation for its conformational analysis of a target molecule is essential. In this project, a new methodology for determination of absolute configuration without its theoretical calculation has been developed by utilizing a huge bisignate VCD signal caused by their interaction of two IR functional groups such as carbonyl groups in a target molecule.
  This novel methodology named as “VCD exciton chirality method” has been applied to a variety of carbohydrates, steroids, complex natural products, acyclic biological active lipids, and poly lactic acid as a polymer, which shows its high applicability.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 24310151
• Studies on the Relationship between the Triple Helical Structure and Immunostimulatory Activity of beta-glucan
  Grants-in-Aid for Scientific Research
  2011 - 2013
  TANIGUCHI Tohru
  The secondary and higher-order structure of oligo- and polysaccharides has been suggested to be important in exhibiting their biological activity; however, few methods have been available to study their relationship. In this study, through basic studies on vibrational circular dichroism (VCD), we developed a "VCD exciton chirality method", which allowed us to study stereostructures of complex molecules. By using this method, we successfully detected the conformational changes of beta glucan triple helix. Aiming at identifying the minimum structure of beta glucan to form triple helix, we also developed a new method to synthesize short beta glucan.
  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 23710244
• βー1,3ーグルカンの高次構造に着目したVCD・合成・免疫学研究
  科学研究費助成事業
  2010 - 2011
  谷口 透
  海藻やキノコに含まれるβ-1,3-グルカンは免疫賦活剤や抗がん剤として臨床に用いられているものの、その特異な三重らせん高次構造のために詳細な分子作用機序は不明である。本研究では、(1)VCD(赤外領域円二色性)を用いた糖鎖高次構造解析法の確立、(2)β-1,3-グルカンフラグメントの有機合成および各フラグメントの三重らせん形成能の検討、(3)得られた三重らせんフラグメントの高次構造と免疫活性化能の相関検討、を行う。本研究の達成により今後、NMRや共結晶を用いたβ-1,3-グルカンとその標的タンパク質との詳細な相互作用の解析を行うことも可能となり、より生理活性の高いβ-1,3-グルカン誘導体の開発、ならびに新規デリバリー法開発に資すると期待される。
  β-1,3-グルカン研究における問題点として、多糖の高次構造を解析する有効な手法が確立されていないことが挙げられる。そこで本研究ではまず、VCDによる多糖の高次構造解析法の開発に着手した。カードラン、シゾフィランなどのβ-1,3-グルカンのVCDを各種条件下で測定したところ、VCDが多糖の高次構造解析に有効であるという予備的知見を得た。これは、VCDを多糖の高次構造解析に用いた初の研究例であり、本手法が多糖全般の高次構造理解の深化に資すると期待される。
  また、β-1,3-グルカンフラグメントの効率的新規合成法の開発に着手した。本研究では、G1cβ1→3G1cβ1→[G1cβ1→3]G1cのような分岐度0.33の4糖ユニットをまず合成し、これをベースに8糖、16糖、24糖などの合成を検討している。平成22年度では、基本となる4糖ユニットの合成に着手し、各種反応条件を最適化してきた。今後、これらのユニットを結合させる各種グリコシデーション法を検討し、合成を達成し、VCD研究ならびに免疫賦活活性試験に供したいと考えている。
  日本学術振興会, 研究活動スタート支援, 北海道大学, 22810002
• 生物によるキラル円偏光識別とその分子機構の解明
  科学研究費助成事業
  2008 - 2010
  門出 健次, 谷口 透
  本研究では、「生物がキラルな円偏光を識別するか?」という単純な命題を明らかにすることを目的としている。昨年度は緑藻クラミドモナスに着目し、企業と共同開発した円偏光装置を用いて「増殖」の様子を観察したが、左右の円偏光で顕著な差は観察されなかった。従って本年度は、クラミドモナスの「走光性」及び「光合成活性」に着目し実験を行った。
  1)円偏光照射対象生物であるクラミドモナスは弱光に対しては近づき(正の走光性)、強光からは逃げる(負の走光性)性質をもつ。本現象にはキラルな光受容体「ロドプシン」が関与しており、左右の円偏光で発色団の光異性化効率に差異が出る可能性がある。本性質に対する円偏光の効果を調査するため、本年度は植物生物学者と共に新たな実験系の確立を行った。実際ODの変化により走光性を観察したところ、左右で走光性に顕著な違いは見られなかった。これはロドプシンにおいて左右円偏光吸収強度の差が極めて小さいためと考えられる。
  2)前年度に左右円偏光でクラミドモナスの増殖に違いが出ないことを確認したが、光合成と増殖は必ずしもリニアな関係に無いことから、本年度はクラミドモナスの光合成に対する円偏光の効果を調査した。本学低温科学研究所の研究者の協力のもと、円偏光照射時の光合成活性を測定し、円偏光の方向性が光合成に与える影響を調査した。結果、光合成活性には差が出ないことがわかった。
  3)円偏光照射対象生物を拡大し、シアノバクテリアについても同様の実験が可能か検討した。本バクテリアはクラミドモナスとは別の光受容体を有することから、異なる応答が期待されたが、クラミドモナスと同様顕著な差は観測されなかった。本年度は左右円偏光を識別する生物、生命現象の発見には至らなかったが、上記実験は世界で初めての試みであり、今後の大きな知見になると考えている。
  日本学術振興会, 挑戦的萌芽研究, 北海道大学, 20651055
• Construction of the standard chiroptical analysis method by vibrational circular dichroism
  Grants-in-Aid for Scientific Research
  2008 - 2010
  MONDE Kenji, MIURA Nobuaki, TANIGUCHI Tohru, MIURA Nobuaki
  Glycerolipids are essential substances for sustaining our life. Although the number of their chiral carbon is only one like most of amino acids, their stereochemistry has not been assigned with ease. In order to establish a new analytical method for determination of their absolute configurations, optically pure glycerolipids and related compounds were prepared by chemical synthesis, and subjected to the "Vibrational Circular Dichromism" measurement. The precise analysis of their spectral data resulted in a discovery of an empirical rule on the stereochemistry of diacylglycerolipids including glycolipids for the first time.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20310127