Vol. 7, Issue 2, Part E (2025)

Peptidomimetic agents are synthetic compounds engineered to mimic the structure and biological functions of natural peptides, but with improved pharmacokinetic properties such as enhanced stability, activity, and bioavailability. Despite the therapeutic success of natural peptides, limitations including low metabolic stability, poor solubility, and challenging delivery have hampered their widespread clinical utility. Peptidomimetics overcome these drawbacks through chemical modifications, including backbone alterations and the incorporation of non-natural amino acids, thereby offering superior resistance to enzymatic degradation and tailored biological activities. This review explores the classification of peptidomimetics, advances in their design strategies, and methodologies for backbone and side-chain modification, as well as their major pharmacological applications. An emphasis is placed on their promise in anticancer, antiviral, and antibacterial therapies, with examples of compounds in preclinical and clinical development. The evolution of peptidomimetics marks a transformative direction for modern drug discovery and therapeutic intervention.