Site-directed Chemical Modification of Phage Particles
The ability to chemically modify the surface of bacteriophage bypasses the functional limitations imposed by the standard biosynthetically incorporated amino acids that comprise the phage coat. Appended functionalities can include fluorescent or other reporter groups, inorganic materials, cytotoxic agents, and pharmacophores. Applications include incorporating the modification in the context of a displayed random peptide library prior to panning as a route to chimeric semisynthetic peptide ligands, use of phage as a template for construction of novel nanomaterials, direct mechanical manipulation of phage, use of phage particles as medical imaging reagents, and catalysis-based screening for novel enzyme activities.
Site-specific modification of phage in the context of the forest of competing functional groups that make up the phage coat requires a uniquely reactive chemical group specifically placed in the coat protein. The so-called “21st amino acid” selenocysteine (Sec) is found in all three kingdoms of life and is co-translationally incorporated