Research

“Between Concept and Reality” — Creating New Research Themes through Chemistry

Why is chemistry called the “Central Science”? Because it acts as an interface that bridges the “in-between” of disciplines at the resolution of atoms and molecules.

The development of excellent drugs and materials, for example, can be described as “creating high-performance substances that serve human society, based on an understanding of the order of nature and life.” The innovative substances and ideas that enrich our lives have always emerged through this process, in response to the needs of their time.

Today, individual fields have become highly specialized and mature. That is precisely why we are now called upon to remove the boundaries between fields, fill the gaps, and create new synergies.

Connecting disciplines through chemistry. We believe this is the starting point for unlocking the full potential of chemistry and making our world broader and richer.

“Between Natural and Artificial” — Reaction Chemistry toward Proteomimetics

Shin-Ichi Fukuoka’s bestseller Between Life and Nonlife describes life in terms of “dynamic equilibrium”: the essence of life lies in the dynamism of matter in constant change. Reaction chemistry, centered on molecules, is the foundation for understanding and controlling such phenomena.

Natural molecules, refined over a long course of evolution, possess complex and sophisticated functions and a biocompatibility that artificial materials lack. Yet they do not always show the functions we need. To turn them into more useful substances, we need technologies that freely modify their structures and create “natural product mimetics” lying between the natural and the artificial.

Until now, modification of natural scaffolds has relied mainly on adding “decorations”; rebuilding the scaffold itself has remained difficult, because methods to freely transform stable, hard-to-modify bonds such as C–C and amide bonds are still lacking.

Our laboratory aims to overcome this barrier and create next-generation biocompatible materials: proteomimetics.

Specifically, we are pursuing:

• Protein backbone editing: new methods to modify and edit the main chains of peptides and proteins

• Reliable ligation: technologies to freely join peptides and proteins

• Function and implementation: advancing our own “protein-decorating” technologies to evaluate and apply the new substances we create

By crossing the boundary between natural and artificial and rebuilding the dynamism of life through chemistry, we aim to open up a new materials science that contributes to future medicine and industry.

“Between Fundamentals and Implementation” — Bringing N-to-C Peptide Synthesis to Society

The market for peptide drugs is expanding rapidly, but conventional manufacturing consumes large amounts of protecting groups and organic solvents, making cost and waste reduction major challenges.

To address this, we established inverse (N-to-C) peptide synthesis using peptide thioacids as key intermediates. The method enables efficient iterative chain elongation while minimizing the use of protecting groups (Commun. Chem. 2023, 6, 231).

We are now working toward practical use in several projects, including a NEDO program for young researchers, to establish it as a next-generation manufacturing technology that achieves lower cost, less waste, and large-scale supply at the same time.

Pursuing academic novelty while turning it into technology that industry actually uses — bridging that gap and accelerating implementation is, we believe, an important part of our role as researchers.

“Between Molecule and Function” — Creating New Biofunctional Materials

Mature techniques for making molecules do not, by themselves, produce excellent “functions.” To realize materials that work as intended in living systems, the gap between molecular structure and biological function must be bridged by precise chemistry.

We have developed techniques to “decorate” proteins — reactions that selectively modify specific amino acid residues such as tryptophan and tyrosine. Recently, we have been exploring mild methods that add functions without damaging biomolecules, such as electrochemical tryptophan-selective modification in neutral buffer.

These methods enable precise biofunctional molecules that were previously hard to make, such as homogeneous antibody–drug conjugates (ADCs) with defined modification sites and numbers, and gold-cluster-labeled antibodies.

Our targets go beyond proteins: we are also developing techniques to selectively label the surfaces of exosomes (vesicles released by cells), as well as functional peptides based on our proprietary methods for manufacturing special peptides.

Furthermore, at the AIST–University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), we combine functional analysis of bioresource-derived materials with chemical transformation technologies, aiming for implementation across medicine, diagnostics, food, and materials.

The “molecules” created by reaction chemistry, and the “functions” exerted in living systems — our goal is to realize, one by one through chemistry, the substances that fill the gap between them.