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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 and Kalbitzer, Hans Robert (2012) Metal–Bis(2-picolyl)amine Complexes as State 1(T) Inhibitors of Activated Ras Protein. Angewandte Chemie International Edition 51, pp. 10647-10651.

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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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Item type:Article
Date:2012
Institutions:Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer
Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König
Projects:DFG
Identification Number:
ValueType
22996816PubMed ID
Keywords:conformational dynamics · drug design · Ras protein · signal transduction
Dewey Decimal Classification:500 Science > 540 Chemistry & allied sciences
Status:Published
Refereed:Yes, this version has been refereed
Created at the University of Regensburg:Yes
Item ID:26541
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