Synthesis and cell-based screening of one-bead-one-compound peptide libraries.

Combinatorial one-bead-one-compound (OBOC) peptide library screening has proven to be a powerful tool for identification of small molecules, peptides, or peptidomimetics against a variety of specific targets such as cell surface receptors, protein kinases, proteases, and phosphatases. With each bead displaying many copies of a single chemical entity, millions of compounds can be rapidly synthesized and screened with whole-cell binding on-bead functional assays. Here we describe the methodology for the synthesis, screening, and sequence deconvolution of an OBOC peptide library analyzed for affinity to a cancer cell line.