Projektnummer

0051567

Zusammenfassung

In the first funding period, different metal cyclen complexes were characterized which can serve as lead compounds shifting the conformational equilibrium from the effector-binding state of Ras to its weak binding state. The influence of these compounds on the conformational equilibrium was studied by 31P-NMR spectroscopy on appropriate effector loop Ras-mutants. ITC experiments and fluorescence spectroscopy showed that these compounds are able to inhibit the binding of the effector Raf-kinase to activated Ras. The structure of the complex of metal-cyclen bound to activated Ras was so...