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Metal-bis(2-picolyl)amine complexes as state 1(T) inhibitors of activated Ras protein
Ina C Rosnizeck1, Michael Spoerner, Tobias Harsch
1Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
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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