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

Rosnizeck, Ina C. ; Spoerner, Michael ; Harsch, Tobias ; Kreitner, Sandra ; Filchtinski, Daniel ; Herrmann, Christian ; Engel, Daniel ; König, Burkhard ; Kalbitzer, Hans Robert



Abstract

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 Zn(2+) -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


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