A fisherman's tale: Phage display as a discovery tool

Extract: Genome sequencing efforts have produced a wealth of information that remains to be exploited at the protein level. A major area of drug discovery involves the identification of novel peptide ligands which could provide leads for the development of new drugs that mimic the structure and function of proteins. These drugs could be used to modulate the activity or interaction of proteins in cells. In biochemistry, ligand refers to a small molecule that binds to a larger macromolecule. Phage surface display, using viruses that infect bacteria called bacteriophages, is a technique where fragments of foreign peptides are joined to the virus proteins and displayed on the phage surface coat, thus maintaining the spatial structure and activity of the protein, and allowing for its exposure to potential interactors or ligands. Both the genetic information and the phenotype are contained within the phage particle allowing for the peptide sequence to be deduced from the DNA sequence. The technique can be used to analyze the molecular recognition properties of peptides and proteins and to identify new ligands for a protein of interest. This would allow for the study of how proteins recognize each other, such as antibody-antigen epitopes (binding sites) and the isolation of biologically active molecules or novel peptide drugs. It can also be used to isolate new antibodies from antibody libraries or identify new substrates for enzymes.