The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Hiroaki Suga 교수의 연구실은 고유한 구조적 특성을 지닌 사이클릭 펩타이드를 설계하고, mRNA 디스플레이와 *in vitro* 번역 기반 선택 기반 기술을 활용해 암 관련 타겟 단백질, 특히 K-Ras와 같은 난이도 높은 단백질-단백질 상호작용 억제제를 개발하는 데 주력하고 있습니다. 비정상적인 아미노산을 포함한 펩타이드의 리보좀 기반 합성 기술을 통해 구조적 다양성을 가진 약물 후보 물질을 창출하는 데도 기여하고 있으며, 이는 신약 개발의 새로운 길을 제시하고 있습니다. 특히, 항체 수준의 친화도를 가지는 사이클릭 펩타이드를 자연물 유사 구조로 설계·도출하는 데에 핵심 기여를 하고 있습니다.
Figures are computed from collected data and may differ slightly.
The past two decades have witnessed the emergence of macrocycles, including macrocyclic peptides, as a promising yet underexploited class of de novo drug candidates. Both rational/computational design and in vitro display systems have contributed tremendously to the development of cyclic peptide binders of either traditional targets such as cell-surface receptors and enzymes or challenging targets such as protein-protein interaction surfaces. mRNA display, a key platform technology for the disco
Studies of the fundamental nature of RNA catalysis and the potential mechanism of a shift from the "RNA world" to proteinaceous life lead us to identify a set of ribozymes (flexizymes) capable of promiscuous tRNA acylation. Whilst theoretically and mechanistically interesting in their own right, flexizymes have turned out to have immense practical value for the simple synthesis of tRNAs acylated with unusual amino acids, which in turn can be used for the ribosomal synthesis of peptides containin
We report the identification of three cyclic peptide ligands of K-Ras(G12D) using an integrated <i>in vitro</i> translation-mRNA display selection platform. These cyclic peptides show preferential binding to the GTP-bound state of K-Ras(G12D) over the GDP-bound state and block Ras-Raf interaction. A co-crystal structure of peptide KD2 with K-Ras(G12D)·GppNHp reveals that this peptide binds in the Switch II groove region with concomitant opening of the Switch II loop and a 40° rotation of the α2
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