Synthetic Auxin with 1000-fold Stronger Binding Affinity than the Natural Auxin

　A technique to induce degradation of target protein which has AID tag for binding to auxin, because auxin receptor protein (TIR1) acts as a F-box protein constituting SCF complex in ubiquitin-proteasome system is called Auxin-inducible degron (AID) system (Figure 1).¹⁾ 5-Adamantyl-IAA (1) has 1000-fold stronger affinity with modified TIR receptor protein than natural auxin.²⁾ These make it possible to induce protein degradation in 1/1000 concentration auxin of original AID system, and a low toxic protein degradation has been reported in mouse and human cells.³⁾

References

• 1) An auxin-based degron system for the rapid depletion of proteins in nonplant cells
• K. Nishimura, T. Fukagawa, H. Takisawa, T. Kakimot, M. Kanemaki, Nat. Methods 2009, 6, 917.
• 2) A Super Strong Engineered Auxin–TIR1 Pair
• R. Yamada, K. Murai, N. Uchida, K. Takahashi, R. Iwasaki, Y. Tada, T. Kinoshita, K. Itami, K. U. Torii, S. Hagihara, Plant Cell Physiol. 2018, 59, 1538.
• 3) A super-sensitive auxin-inducible degron system with an engineered auxin-TIR1 pair
• K. Nishimura, R. Yamada, S. Hagihara, R. Iwasaki, N. Uchida, T. Kamura, K. Takahashi, K. U. Torii, T. Fukagawa, Nucleic Acids Res. 2020, 48, 108.

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