Mutations in codon 12, 13, or 61 convert H-ras, K-ras, and N-ras into oncogenes. Such mutationally activated Ras proteins are found in about 30% of human tumors. Despite their medical importance, specific therapeutic agents directly targeting Ras proteins have not yet been discovered. To develop such Ras inhibitors, we have identified peptide aptamers that interact with oncogenic RasV12 from human tumors. Furthermore, we have demonstrated that these peptide aptamers inhibit the Ras/Raf signal transduction pathway in mammalian cells. Moreover, we have shown that these Ras peptide aptamers inhibit tumor growth in vitro and in mice bearing human tumor xenografts. Here, we propose to further characterize: 1. Peptide aptamers that inhibit Ras functions. 2. Peptide aptamers that interact with oncogenic Ras. 3. Peptide aptamers that inhibit tumorigenesis. These studies provide a new systematic framework for developing inhibitors of any proteins of biological and/or medical importance.
|Yamazaki, Hiroto; Xu, C Wilson; Naito, Motohiko et al. (2011) Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia. Biochem Biophys Res Commun 409:14-21|