The primary goal of this project in this NCDDG is to identify peptide ligands that bind specifically to tumor-associated-receptor molecules (e.g. epidermal growth factor receptor (EGFR), p185 HER2/neu """"""""receptor"""""""" protein (HER2R), p145 c-kit """"""""receptor"""""""" (c-kitR), and FGF receptor (FGFR) and other growth factor receptors. Based on this discovery phase for peptide leads, we plan to design and test potent antagonists that have cytotoxic or cytostatis effects on tumor cell growth. We will use the random peptide library synthesis and screening (""""""""Selectide"""""""") technology for screening libraries for such peptide leads. In these studies, large libraries containing 106-107 peptides will be synthesized in project 1 by Dr. Lebl such that each resin bead contains single peptide entity. Each library of beads is then mixed with a """"""""tagged"""""""" acceptor molecule (e.g. EGFR). Ligand beads that bind acceptor molecules are identified by staining with an enzyme-catalyzed color reaction. The stained beads are then physically isolated and the peptide sequence on each individual bead determined by Edman degradation using an automatic protein sequenator. The overall medical impact of this project will be to markedly shorten the discovery phase for receptor binding peptides and thereby provide strong leads for anticancer drug development.
| Salmon, S E; Liu-Stevens, R H; Zhao, Y et al. (1996) High-volume cellular screening for anticancer agents with combinatorial chemical libraries: a new methodology. Mol Divers 2:57-63 |
| Nikolaiev, V; Stierandova, A; Krchnak, V et al. (1993) Peptide-encoding for structure determination of nonsequenceable polymers within libraries synthesized and tested on solid-phase supports. Pept Res 6:161-70 |
