Peptide Discovery: Lead Generation

Peptide therapeutics have emerged as a significant segment of the pharmaceutical market, with 80 FDA-approved peptide drugs and over 170 peptides in active clinical development. Historically viewed as complex and costly to develop, peptides were once primarily used as tools in drug discovery rather than as therapeutic agents. However, key scientific achievements, including the isolation of insulin and advances in peptide synthesis technologies, such as solid-phase peptide synthesis and native chemical ligation, have revolutionized the field. These innovations have facilitated the high-speed, high-yield production of peptides and the assembly of complex peptide and protein sequences, paving the way for their successful application in therapy. Recent advancements in peptide hit discovery and lead generation have further accelerated the growth of peptide therapeutics. The exploration of natural peptides, screening of artificial peptide libraries, and computational design are three major strategies employed in this field. Naturally occurring peptides, and analogs thereof, have inspired many marketed drugs, while display technologies, artificial libraries, and novel computational tools have expanded the scope for discovering new peptide therapeutics. This chapter will examine approaches to peptide hit discovery, highlighting how these strategies, coupled with advancements in drug delivery and synthesis, are expected to increase the number of approved peptide drugs in the coming years.