Identification and characterization of a peptidic ligand for Ras.
The development of new ligands for the oncoprotein Ras can provide tools for the study of this important signaling component or potentially serve as therapeutic agents for the treatment of Ras-associated diseases. Herein, we report a peptidic Ras ligand identified through naïve phage display. Panning a phage library with a diversity of 10(9) transormants successfully identified a peptide dodecamer that contains two internal consensus motifs and binds Ras in both the active GTP- and inactive GDP-bound conformations with low micromolar dissociation constants. The dodecamer does not alter the intrinsic GTPase activity of Ras, does not compete for Ras binding to the Ras binding domain of Raf, and does not alter cell viability. This novel Ras ligand has the potential to serve in the development of higher-affinity ligands and chemical tools targeting Ras.
Gareiss
Peter C
PC
Department of Molecular, Cellular & Developmental Biology, Yale University, P. O. Box 208103, New Haven, CT 06520-8103, USA.
Schneekloth
Ashley R
AR
Salcius
Michael J
MJ
Seo
Seung-Yong
SY
Crews
Craig M
CM
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism*
D019151:Peptide Library; D010455:Peptides; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D018631:ras Proteins