Synthesis and screening of a 'one-bead-one-compound' combinatorial peptide library

By using a 'split-synthesis' method in conjunction with standard solid- phase peptide synthesis, a library of peptide beads can be synthesized so there is only one unique peptide species on each bead-the 'one-bead-one- compound' concept. With an appropriate screening method targeted for a specific biological, physical, or biochemical property, a unique peptide bead can be identified, physically isolated, and the peptide structure determined. The screening method may involve (1) on-bead assay such as direct binding or covalent modification or (2) releasable assay in which the peptides are released from the bead for biological or biochemical testing. Examples of these methods for various targets will be described. This one-bead-one- peptide library method enables one to synthesize and screen 10⁷ unique peptides routinely and rapidly and has proved to be an invaluable tool for basic research and drug discovery.