CHAPTER 9: Libraries of Head-to-tail Peptides

Head-to-tail cyclic peptides are an emerging class of compound that show promise against targets considered challenging for small molecules, such as protein–protein interactions. Encouraged by the bioactivity of natural product examples, efforts have been made to develop novel therapeutics through high-throughput screening platforms. A key component of this approach is the efficient generation of compound libraries to utilize with them. Libraries of head-to-tail peptides may be generated by chemical synthetic or genetically derived means. Whilst these techniques are currently commonly used for linear peptide libraries, head-to-tail cyclization presents an additional challenge and therefore specialized methods in the fields of both chemistry and biology have been developed to access this class of compound. This chapter considers the preparation, application, deconvolution and functional diversity of libraries generated via these techniques.