title: Sequence-selective molecular recognition of the C-terminal CaaX-boxes of Rheb and related Ras-proteins by synthetic receptors.
abstract: 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.
authors.affiliation: University of Wuppertal , Gaußstraße 20, D-42119 Wuppertal, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Düppe
authors.forename: Thao
authors.initials: T
authors.lastname: Tran Thi Phuong
authors.forename: Jasmin
authors.initials: J
authors.lastname: Autzen
authors.forename: Miriam
authors.initials: M
authors.lastname: Schöpel
authors.forename: King Tuo
authors.initials: KT
authors.lastname: Yip
authors.forename: Raphael
authors.initials: R
authors.lastname: Stoll
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scherkenbeck
mesh_terms: D013058:Mass Spectrometry; D008958:Models, Molecular; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013056:Spectrophotometry, Ultraviolet; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins