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Metal–Bis(2-picolyl)amine Complexes as State 1(T) Inhibitors of Activated Ras Protein


  • This work was supported financially by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the Volkswagenstiftung. We thank Georg Discherl and Florian Schmidt for the synthesis of the M2+–BPA complexes.


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Allosteric interactions: Metal(II) cyclens inhibit Ras–effector interactions by stabilizing a weak effector-binding state of Ras, state 1(T), and binding directly in the active site. The novel state (1T) inhibitor Zn2+–BPA (BPA=bis(2-picolyl)amine) binds outside the nucleotide binding pocket but nevertheless allosterically stabilizes state 1(T) and thus inhibits the Ras–Raf interaction.