This laboratory program in this NCDDG is designed to facilitate discovery of new peptides with anticancer activity using an entirely new cellular screening assay designed for use with synthetic peptide libraries prepared with a variant of the selectide process. The specific variant technology permits release of separated subsets of peptides into solution to be tested against a panel of human tumor cell lines while still retaining sufficient peptide on the bead to permit sequence determination of just those beads which release potent antitumor peptides. Tumor types of priority in this project include cancers of the breast, colon, lung, prostate, melanoma and leukemia. A specific screening logic and testing system has been devised to permit rapid screening of a series of libraries containing 105-106 peptides to identify those with antitumor activity. This laboratory program will also retest peptides and related compounds identified or developed in the other projects in this NCDDG and therefore represents a key in vitro testing resource for the program. Those compounds which demonstrate discrete and selective anticancer activity against one or several tumor types will be given high priority for further drug development through this NCDDG, and beyond that by the NCI and the Selectide Corporation. Our overall longterm objective is therefore to identify new peptidic agents with antitumor activity as a key step in their development as new anticancer drugs that are effective against major forms of human cancer.
| 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 |
