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2023 Fiscal Year Annual Research Report

抗KRAS環状ペプチドファマコフォアの小型タンパク質へのラソグラフト体の創出

Research Project

Project/Area Number 22KF0089
Allocation TypeMulti-year Fund
Research InstitutionThe University of Tokyo

Principal Investigator

菅 裕明  東京大学, 大学院理学系研究科(理学部), 教授 (00361668)

Co-Investigator(Kenkyū-buntansha) COLAS KILIAN  東京大学, 大学院理学系研究科(理学部), 外国人特別研究員
Project Period (FY) 2023-03-08 – 2024-03-31
Keywordsprotein engineering / grafting / KRas / peptide
Outline of Annual Research Achievements

We have identified 20 lasso-grafted peptides, termed “Ubodies”, that target one of the major cancer-drivers, KRas(G12D). Some compounds bind to the protein target with high selectivity towards the cancer-driver “on” state of KRas vs its “off” state; while others are selective towards the mutant form vs its wildtype parent (some compounds exhibit dual selectivity). These Ubodies thus have high potential as therapeutic candidates with very little side-effects. Furthermore, we have also developed a new method to identify de novo highly potent Ubodies without the need for a previous binding peptide, which we are currently applying to other cancer targets. We have also started investigating drug delivery avenues (lipid nanoparticles & gene delivery), and early protocols are being validated.

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Published: 2024-12-25  

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