From synthetic methods to peptide-based drugs in three integrated sections Peptides offer high potency and target specificity, yet low metabolic stability limits their direct therapeutic use. Peptidomimetics in Drug Discovery presents an integrated approach to overcoming these limitations through synthetic methodology, scaffold design, and medicinal chemistry applications. Organized in three logical sections, the book progresses from foundational concepts and chemistry toolbox development through scaffold construction to successful case studies of approved peptide-based drugs. Detailed coverage spans unnatural amino acid chemistry, amino acid-side chain isosteres, backbone and dipeptide isosteres, cyclic scaffolds, foldamers, macrocyclic peptidomimetics and stapled peptides. Hit-to-lead case studies feature the development of nirmatrelvir, the peptidomimetic SARS-CoV-2 antiviral, alongside therapeutic applications in CNS disorders and cancer. The book also covers: Bioisosterism principles applied to peptide bond replacement and their role in optimizing pharmacokinetic properties of lead compoundsScaffolds for combinatorial chemistry of peptidomimetics enabling systematic exploration of chemical space around peptide-derived structuresConcepts linking computational chemistry and biophysics to rational peptidomimetic design for target-specific drug candidatesPractical approaches to improving molecular stability and bioavailability while retaining the biological activity of parent peptide sequencesStrategies connecting early-stage hit identification with lead optimization through structure-activity relationships in peptidomimetic drug development Peptidomimetics in Drug Discovery serves researchers in academia and industry working across medicinal chemistry, pharmaceutical research, and peptide-based drug development. It is equally relevant to postgraduates and investigators in computational chemistry, biophysics, and biomedical research seeking to advance peptide-derived lead compounds toward therapeutic application.
