Sequence-Selective Molecular Recognition of the C-Terminal CaaX-Boxes of Rheb and Related Ras-Proteins by Synthetic Receptors (original) (raw)

Constitutive activation of Ras-proteins plays an important role in the development of aggressive colorectal carcinomas and several other types of cancer. Despite some progress in recent years in the case of K-Ras4B, until now not a single small molecule inhibitor has been identified that binds efficiently to Rheb and interrupts the protein−protein interactions with mTOR. We describe here a complementary approach that aims at inhibiting membrane insertion of Rheb and related Ras proteins by masking the crucial C-terminal CaaX-box with peptidomimetic receptors identified in combinatorial solid-phase libraries.