title: Structure-based design of peptidomimetic ligands of the Grb2-SH2 domain.
abstract: We have designed and synthesized a (3-aminomethyl-phenyl)-urea scaffold to mimic the X+1-Asn part of the minimal phosphopeptide sequence, Ac-pTyr-X+1-Asn-NH2, recognized by the Grb2-SH2 domain. The resulting compounds show the same degree of affinity as their peptide counterparts for the Grb2-SH2 domain. This is the first example reported to date of ligands of the Grb2-SH2 domain with substantially reduced peptidic character.
authors.affiliation: Novartis Pharma Inc., Oncology Research Department, Basle, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schoepfer
authors.forename: B
authors.initials: B
authors.lastname: Gay
authors.forename: G
authors.initials: G
authors.lastname: Caravatti
authors.forename: C
authors.initials: C
authors.lastname: Garcia-Echeverria
authors.forename: H
authors.initials: H
authors.lastname: Fretz
authors.forename: J
authors.initials: J
authors.lastname: Rahuel
authors.forename: P
authors.initials: P
authors.lastname: Furet
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051380:GRB2 Adaptor Protein; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D010748:Phosphopeptides / Q000737:chemistry* / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D008024:Ligands; D010748:Phosphopeptides; D011506:Proteins; D066246:ErbB Receptors