2022年7月2日 16:10～17:10 沖縄コンベンションセンター 劇場棟 第1会場
3S01e-01
自己集合体のケミカルバイオロジー
Chemical Biology of Self-Assemblies
*上杉 志成(1,2)
1. 京都大学化学研究所、2. 京都大学WPI-iCeMS
*Motonari Uesugi(1,2)
1. Kyoto University, 2. Kyoto University WPI-iCeMS
Keyword: self-assembly, chemical biology, immune response, glucose
A defining characteristic of living organisms is the ability to form hierarchical structures that allow them to perform complex, versatile biological processes. At the heart of these hierarchical structures is molecular self-assembly, which is defined as the spontaneous self-organization of molecules to form non-covalent structures. Examples of the naturally-occurring self-assembly structures include nucleic acids, membrane and membrane-less organelles, and protein filaments. We envisioned that these biological assemblies could be controlled or mimicked by self-assembling small molecules. Such molecules would implicate new ways of modulating biological systems that are not amenable to conventional small molecules.
This presentation showcases unique self-assembling small molecules we discovered from the screening of chemical libraries. Once assembled, these molecules control cell proliferation, cell adhesion, ER stress, and immune responses, respectively (1-5). Molecular understanding of their mechanisms of actions led to the design of self-assembling molecules that could potentially be used both for basic cell biology and for therapeutic applications.
At the end of the presentation, our recent discovery of glucose as a protein-condensing cellular solute will also be discussed (6). Proteomic analysis identified a number of cellular proteins that displayed robust glucose-dependent precipitation. Our findings suggest that glucose is a heretofore underappreciated driver of protein phase separation that may have profound effects on cellular homeostasis. I hope that the presentation will be able to expand the collaborations with neuro scientists.
References
1. Small molecule-induced clustering of heparan sulfate promotes cell adhesion. Takemoto, N. et al. J. Am. Chem. Soc. 135 (30), 11032−11039 (2013).
2. Synthetic molecules that protect cells from anoikis and their use in cell transplantation. Frisco-Cabanos, H.L. et al. Angew. Chem. Int. Ed., 53 (42), 11208-11213 (2014).
3. Multifunctionalization of Cells with a Self-Assembling Molecule to Enhance Cell Engraftment. Takashima, I. et al. ACS Chem. Biol., 14(4), 775–783 (2019).
4. Discovery of Self-Assembling Small Molecules as Vaccine Adjuvants. Jin, S. et al. Angew. Chem. Int. Ed. 60(2), 961-969 (2021).
5. Discovery of a Phase-Separating Small Molecule That Selectively Sequesters Tubulin in Cells. Ado, G. et al. Chem. Sci. in press (2022).
6. Glucose as a Protein-Condensing Cellular Solute. Noda, N.et al. ACS Chem. Biol. in press (2022). | | 2022年7月2日 17:10～18:10 沖縄コンベンションセンター 劇場棟 第1会場
3S01e-02
超分子化学から神経化学へ
Neurochemistry from supramolecular chemistry
*村岡 貴博(1,2)
1. 東京農工大学グローバルイノベーション研究院、2. （地独）神奈川県立産業技術総合研究所
*Takahiro Muraoka(1,2)
1. Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2. Kanagawa Institute of Industrial Science and Technology (KISTEC)
Keyword: self-assembly, peptide, ion channel, regenerative medicine
Supramolecular chemistry is a research area that elucidates the mechanism of molecular assembly and develops materials made of self-assembled molecules. Since biomolecules and tissues are constructed by supramolecular systems through organized molecular assemblies, approaches from supramolecular chemistry are expected to be useful and effective for controlling biological activities and designing regenerative medicines. Recently we have developed synthetic supramolecular ion channels that respond to ligands. Inspired by the molecular structures of multipass transmembrane proteins, amphiphiles consisting of repeating motifs between hydrophobic and hydrophilic domains have been synthesized. The amphiphiles could be inserted into the plasma membrane of living cells in a uniformly oriented manner. Ion transportation function was activated upon the addition of ligands such as phenethylamine to allow for trimeric assemblies and trigger calcium ion flow into the cells. To develop bioinspired regenerative medicines, we have constructed peptidic supramolecular nanofibers as a synthetic mimic of extracellular matrices (ECM). The peptidic nanofibers showed a cell adhesion property. To endow the nanofibers with the sustained-release function of growth factors to facilitate tissue regeneration, we also synthesized vascular endothelial growth factor (VEGF) conjugated with the fiber-forming peptide as an insertion tag. The tagged VEGF was readily and efficiently incorporated into the peptidic nanofibers. Sustained release of the incorporated VEGF was also observed in a physiological condition. By the administration of the cell-adhesive supramolecular peptide nanofibers capable of VEGF releasing, we have successfully demonstrated cell transplantation-free regenerative therapeutic effects in a subacute-chronic phase mouse stroke model. |
