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 compounds
• Scaffolds for combinatorial chemistry of peptidomimetics enabling systematic exploration of chemical space around peptide-derived structures
• Concepts linking computational chemistry and biophysics to rational peptidomimetic design for target-specific drug candidates
• Practical approaches to improving molecular stability and bioavailability while retaining the biological activity of parent peptide sequences
• Strategies 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.

Andrea Trabocchi, PhD, is Associate Professor of Organic Chemistry at the University of Florence, with research focused on bioactive heterocycle synthesis, peptidomimetic chemistry, and enzyme inhibitor development for oncology and Alzheimer's disease. He has published over 100 scientific articles, filed 4 patents, andserves on the advisory board of Chemical Society Reviews. He previously authored Peptidomimetics in Organic and Medicinal Chemistry (Wiley, 2014) and edited two additional volumes on diversity-oriented synthesis and small molecule drug discovery.