Peptide Drug Discovery Raison d’Etre: Engineering Mindset, Design Rules and Screening Tools

Over the last several decades peptide drug discovery has been a source of significant challenge, innovation, and achievement against varying target classes. Noteworthy advances in design, synthesis, and structure-property relationship analysis as well as emerging opportunities for drug delivery, chart the path forward. Herewith we hope to capture the spirit of peptide drug discovery that has been the inspiration of many scientists to advance peptide therapeutic modalities. These have included both linear and macrocyclic peptides, receptor-targeted agonists and antagonists, protease and other enzyme inhibitors, and intracellular protein-protein as well as transcription/translation-targeted modulators. Some noteworthy case studies are exemplified to represent the engineering mindset of key concepts and learnings. Lastly, we share thoughts on what has emerged over recent years in terms of design rules and screening tools that have enabled the raison d’etre of peptide drug discovery: delivering innovative therapies for un-met medical needs.