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Binding and Biological Effect of Small Molecule Ligands to Ramos Lymphoma Cancer Cell Line Proteins

Combinatorial chemistry enables millions of chemical compounds to be generated and screened for their ability to bind to specific macromolecules and induce a biological response. This study aims to use this technological advancement for basic research and drug discovery. Using “one‐bead one‐compound” (OBOC) combinatorial library screening approach, we have identified small molecule ligands that bind to Ramos lymphoma intracellular proteins. The ligand‐beads were sequenced and then resynthesized in a soluble and immobilized form. We investigated if these soluble ligands have biological activity by using them to treat Ramos lymphoma cells in culture. Our findings show that some ligands may inhibit cell growth. Furthermore, these ligands were tested in combination with the chemotherapeutic agent paclitaxel, a highly toxic compound currently used to treat cancer. A few ligands demonstrated a stronger synergistic inhibitory effect with paclitaxel on the proliferation of Ramos cells, compared to the weaker effect shown when they were added separately. With the results of the biological activity that some ligands have on Ramos, we are presently identifying bound Ramos proteins by ligand‐affinity column chromatography and mass spectrometry. In the future, we may use these small molecule ligands to develop a chemical microarray system that can analyze proteins from cancer cells or normal cells and be able to distinguish between the two conditions. This study may help with potential applications of new cancer drug targets to be identified, thereby providing new leads for drug development.