Bacteriophages and Viruses as a Support for Organic Synthesis and Combinatorial Chemistry

Display of polypeptide on the coat proteins of bacteriophages and viruses is a powerful tool for selection and amplification of libraries of great diversity. Chemical diversity of these libraries, however, is limited to libraries made of natural amino acid side chains. Bacteriophages and viruses can be modified chemically; peptide libraries presented on phage thus can be functionalized to yield moieties that cannot be encoded genetically. In this review, we summarize the possibilities for using bacteriophage and viral particles as support for the synthesis of diverse chemically modified peptide libraries. This review critically summarizes the key chemical considerations for on-phage syntheses such as selection of reactions compatible with protein of phage, modification of phage support that renders it more suitable for reactions, and characterization of reaction efficiency.