First experimental identification of Ras-inhibitor binding interface using a water-soluble Ras ligand.
By combining in the same molecule Ras-interacting aromatic moieties and a sugar, we prepared a water-soluble Ras ligand that binds Ras and inhibits guanine nucleotide exchange. With this compound it was possible to determine experimentally by a (15)N-edited HSQC NMR experiment the ligand-Ras binding interface.
Palmioli
Alessandro
A
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, 2, 20126 Milano, Italy.
Sacco
Elena
E
Abraham
Sherwin
S
Thomas
Celestine J
CJ
Di Domizio
Alessandro
A
De Gioia
Luca
L
Gaponenko
Vadim
V
Vanoni
Marco
M
Peri
Francesco
F
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005960:Glucosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006147:Guanine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D041681:NIH 3T3 Cells; D011485:Protein Binding; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D005960:Glucosides; D008024:Ligands; C107861:SCH 54292; D013449:Sulfonamides; D006147:Guanine; D018631:ras Proteins