Hiroaki Suga
Wolf Prize Laureate in Chemistry 2023
Hiroaki Suga
Affiliation at the time of the award:
The University of Tokyo, Japan
Award Citation:
“For developing RNA-based catalysts that revolutionized the discovery of bioactive peptides”.
Prize Share:
Hiroaki Suga
Jeffery W. Kelly
Chuan He
“for pioneering discoveries that illuminate the functions and pathological dysfunctions of RNA and proteins and for creating strategies to harness the capabilities of these biopolymers in new ways to ameliorate human diseases.”
Prof. Suga received his Bachelor of Engineering (1986) and Master of Engineering (1989) from Okayama University, Ph.D. in Chemistry (1994) from MIT, and was a post-doctoral fellow at the Massachusetts General Hospital. Suga began his independent career at New York State University at Buffalo (1997-2003). In 2003 he moved to the Research Center for Advanced Science and Technology at the University of Tokyo. Since 2010 Suga has been a full Professor in the department of chemistry at the University of Tokyo. Currently, he serves as the President of the Chemical Society of Japan.
Prof. Suga’s research interests include bioorganic chemistry, chemical biology, and biotechnology related to RNA, translation, and peptides. As a young researcher, he made significant advances in using RNA-based enzymes, or ribozymes, to incorporate unnatural amino acids into tRNA. This technology, known as the “Flexizyme,” greatly expanded the potential for reprogramming the genetic code. Through additional research on in vitro translation of proteins using reconstituted ribosomes, Prof. Suga could incorporate various unnatural amino acids into expressed peptides to spontaneously produce molecules that form macrocyclic peptides. Prof. Suga used oligonucleotide display and directed evolution to create the RaPID system, a platform for producing and selecting billions of macrocyclic peptides as high-affinity binders to protein targets, including many that had previously been considered undruggable.
In 2006, Prof. Suga co-founded PeptiDream to advance and apply the RaPID system, which quickly became a widely used technology for finding small molecule protein binders, particularly disrupting protein-protein interactions. His discoveries have enabled the construction of complex molecules on a large scale, not possible using conventional methods alone. Suga’s work has produced more unique non-natural molecules than other approachs, which possess the unique stereochemistry, rich functional group density, and 3D-architecture necessary for interrogating and controlling biological processes. This paved the way for a new generation of drugs. PeptiDream became a publicly traded company on the Tokyo Stock Exchange and is one of Japan’s most successful startup companies.
Hiroaki Suga is awarded the Wolf prize for developing an exceptionally innovative in-vitro selection system for cyclic peptides as inhibitors of protein-protein interactions. He invented an RNA-based catalyst, flexizyme, that transcends natural mechanisms and vastly expands the range of amino acids that can be incorporated with ribosomal machinery. Suga’s strategy enables rapid construction and screening of enormous cyclic peptide libraries. His unique discovery has established a new approach to medicinal chemistry and generated new tools for drug discovery.