The Sato Lab develops artificial molecules that mimic the structure and function of biomolecules in living organisms. The following is a brief summary of what we have developed to date.


1. Fluorinated Nanochannels (フッ素化人工チャネル)

The selective permeation of ions and water molecules across cellular membranes by channel proteins is a ubiquitous phenomenon observed in various aspects of biological events.  Inspired by the structures and functions of such channel proteins, our group has developed a series of unique synthetic channels incorporating fluorine atoms, elements rarely found in natural proteins. We have demonstrated that fluorinated nanochannels exhibit anomalous material permeation properties, such as stimuli-responsive selective ion permeation and ultrafast selective water permeation.


(1) Synthetic Ion Channel Formed by Multiblock Amphiphile with Anisotropic Dual Stimuli-Responsiveness

Ryo Sasaki, Kohei Sato*, Kazuhito Tabata, Hiroyuki Noji, Kazushi Kinbara*
J. Am. Chem. Soc. 2021, 143, 1348–1355.

(2) Ultrafast water permeation through nanochannels with a densely fluorous interior surface

Yoshimitsu Itoh*, Shuo Chen, Ryota Hirahara, Takeshi Konda, Tsubasa Aoki, Takumi Ueda, Ichio Shimada, James J. Cannon, Cheng Shao, Junichiro Shiomi, Kazuhito V. Tabata, Hiroyuki Noji, Kohei Sato*, Takuzo Aida*
Science 2022, 376, 738–743.

(3) Supramolecular Mechanosensitive Potassium Channel Formed by Fluorinated Amphiphilic Cyclophane

Kohei Sato*, Ryo Sasaki, Ryoto Matsuda, Mayuko Nakagawa, Toru Ekimoto, Tsutomu Yamane, Mitsunori Ikeguchi, Kazuhito V. Tabata, Hiroyuki Noji, Kazushi Kinbara*
J. Am. Chem. Soc. 2022, 144, 11802–11809.

2. Self-assembling peptides for regenerative medicine

Fibrous extracellular matrices regulate cell growth and differentiation by interacting with cell receptors. In this study, we developed amphiphilic peptides that self-assemble into nanofibers and demonstrated their potential as regenerative medicines. Particularly, when the nanofibers were added to human iPS cell-derived neurons, the nanofibers showed significantly enhanced ability to promote neuronal cell growth compared to natural proteins with similar functions.


(4) Programmable Assembly of Peptide Amphiphile via Noncovalent-to-Covalent Bond Conversion

Kohei Sato, Wei Ji, Liam C. Palmer, Benjamin Weber, Matthias Barz, Samuel I. Stupp*

J. Am. Chem. Soc. 2017, 139, 8995–9000.

(5) Chiral Recognition of Lipid Bilayer Membranes by Supramolecular Assemblies of Peptide Amphiphiles
Kohei Sato, Wei Ji, Zaida Àlvarez, Liam C. Palmer, Samuel I. Stupp*

ACS Biomater. Sci. Eng. 2019, 5, 2786–2792.

(6) Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons
Zaida Álvarez, J Alberto Ortega, Kohei Sato, Ivan R Sasselli, Alexandra N Kolberg-Edelbrock, Ruomeng Qiu, Kelly A Marshall, Thao Phuong Nguyen, Cara S Smith, Katharina A Quinlan, Vasileios Papakis, Zois Syrgiannis, Nicholas A Sather, Chiara Musumeci, Elisabeth Engel, Samuel I Stupp*, Evangelos Kiskinis*
Cell Stem Cell 2023, 30, 219–238.

3. Understanding the mechanisms of refractory neurological diseases

Amyotrophic lateral sclerosis (ALS) is an incurable neuronal disease that causes gradual loss of motor function throughout the body due to nerve degeneration. Recent studies have implicated dipeptide repeat proteins (DPRs) in the disease, but the basic physicochemical properties of DPRs remained largely unknown due to the difficulty of chemically synthesizing DPRs themselves. In this study, we succeeded in chemically synthesizing DPRs consisting of up to 200 amino acid residues using the automated fast-flow peptide synthesis, in which Fmoc-protected amino acids and coupling reagents are pumped at high temperature and high speed onto a peptide resin using a flow device. In addition, the physicochemical properties of the DPRs were elucidated, and the interaction between DPRs and RNA was found to be involved in the pathogenesis of ALS.

筋萎縮性側索硬化症(ALS)は神経の変性によって全身の運動機能が徐々に失われていく難治性疾患です。近年,ジペプチド・リピート(DPR)と呼ばれるタンパク質が疾患に関与していることが明らかになってきましたが,DPR自体の化学合成が困難であるために,その基本的な性質の大部分は未解明でした。本研究では,Fmoc 基で保護されたアミノ酸とカップリング剤をフロー装置によって高温・高速で固相担体へと送液し,担体上におけるカップリング反応の効率を著しく向上させる「固相フロー法」を用いることで,最長で200残基ものアミノ酸が連なったDPRを合成することに成功しましたさらに,得られたDPRの物理化学的性質を解明するとともに,ALSの発症にDPRとRNAとの相互作用が関与していることを明らかにしました。

(7) Automated Fast-Flow Synthesis of Chromosome 9 Open Reading Frame 72 Dipeptide Repeat Proteins

Kohei Sato, Charlotte E. Farquhar, Jacob Rodriguez, Bradley Pentelute*

J. Am. Chem. Soc. 2023, 145, 12992–12997.

(8) CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides against C9ORF72 ALS/FTD poly-GR pathophysiology

Juan A. Ortega, Ivan R. Sasselli, Marco Boccitto, Andrew C. Fleming, Tyler R. Fortuna, Yichen Li, Kohei Sato, Tristan D. Clemons, Elizabeth D. Mckenna, Thao P. Nguyen, Eric N. Anderson, Jesus Asin, Justin K. Ichida, Udai B. Pandey, Sandra L. Wolin, Samuel I. Stupp, Evangelos Kiskinis*
Sci. Adv. 2023, 9, eadf7997.