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
| Project/Area Number |
22KF0089
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| Allocation Type | Multi-year Fund |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
菅 裕明 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
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| 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
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Keywords | protein engineering / grafting / KRas / peptide |
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| 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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