Metal-bis(2-picolyl)amine complexes as state 1(T) inhibitors of activated Ras protein.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION(2012)
摘要
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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关键词
conformational dynamics,drug design,Ras protein,signal transduction
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