Peptide Combinatorial Libraries

Abstract

Peptide libraries, which consist of a few thousands to tens of millions of distinct peptides, can be generated combinatorially through biologic or synthetic approaches. The phage‐display peptide library method is simple and economical, and peptides with various natural protein folds can be generated by this approach; but this biologic method generally is limited to peptides that contain only L‐amino acids. Synthetic combinatorial libraries, however, can accommodate D‐amino acids, unnatural amino acids, and even organic moieties, which makes these approaches highly versatile. These synthetic methods include the spatially addressable parallel library method, the combinatorial library method that requires deconvolution, the one‐bead one‐compound (OBOC) combinatorial library method, the self‐assembled peptide nucleic acid (PNA) encoded chemical microarrays, and the synthetic library method that requires chromatography selection. Various methods to screen these combinatorial libraries have been developed. For example, phage‐display peptide libraries can be screened for the ability of phages to bind to unique immobilized target proteins or whole cells, peptide microarrays can be screened for their ability to interact with fluorescent proteins, combinatorial library methods that require deconvolution can be screened by standard solution‐phase assays, and OBOC libraries can be screened by on‐bead binding or functional assays or several solution‐phase cell‐based or biochemical assays. Combinatorial peptide library methods are enabling technologies that have proven to be very useful in basic research and drug discovery.