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. Pannin...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2010-03, Vol.11 (4), p.517-522
Main Authors: Gareiss, Peter C, Schneekloth, Ashley R, Salcius, Michael J, Seo, Seung-Yong, Crews, Craig M
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Animals
biophysics
Cell Line
Cell Survival
Guanosine Diphosphate - metabolism
Guanosine Triphosphate - metabolism
Humans
Peptide Library
peptides
Peptides - chemistry
Peptides - metabolism
phage display
Protein Conformation
Ras
ras Proteins - chemistry
ras Proteins - metabolism
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Summary: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 10⁹ 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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.200900547