Peptidomimetics design and characterization: Bridging experimental and computer-based approaches

Chapter Get rights and content Chapter Nine - Peptidomimetics design and characterization: Bridging experimental and computer-based approaches Alice Romagnoli a b c , Jesmina Rexha a b c , Nunzio Perta a b c , Samuele Di Cristofano d , Noemi Borgognoni a b c , Gloria Venturini a b , Francesco Pignotti a b , Domenico Raimondo d e , Tiziana Borsello c f , Daniele Di Marino a b c a Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy b New York-Marche Structural Biology Centre (NY-MaSBiC), Polytechnic University of Marche, Ancona, Italy c Neuronal Death and Neuroprotection Unit, Department of Neuroscience, Mario Negri Institute for Pharmacological Research-IRCCS, Milan, Italy d Department of Molecular Medicine, Spienza University of Rome, Rome, Italy e National Biodiversity Future Center (NBFC), Rome, Italy f Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy Available online 25 July 2024, Version of Record 21 March 2025. What do these dates mean? Show less Cite Add to Mendeley Share 10.1016/bs.pmbts.2024.07.002 Access through another organization Article preview Recommended articles Cited by (3) Metrics Article preview Abstract Introduction Section snippets References (224) Abstract Peptidomimetics, designed to mimic peptide biological activity with more drug-like properties, are increasingly pivotal in medicinal chemistry. They offer enhanced systemic delivery, cell penetration, target specificity, and protection against peptidases when compared to their native peptide counterparts. Already utilized in treating diverse diseases like neurodegenerative disorders, cancer and infectious diseases, their future in medicine seems bright, with many peptidomimetics in clinical trials or development stages. Peptidomimetics are well-suited for addressing disturbed protein-protein interactions (PPIs), which often underlie various pathologies. Structural biology and computational methods like molecular dynamics simulations facilitate rational design, whereas machine learning algorithms accelerate protein structure prediction, enabling efficient drug development. Experimental validation via various spectroscopic, biophysical, and biochemical assays confirms computational predictions and guides further optimization. Peptidomimetics, with their tailored constrained structures, represent a frontier in drug design focused on targeting PPIs. In this overview, we present a comprehensive landscape of peptidomimetics, encompassing perspectives on involvement in pathologies, chemical strategies, and methodologies for their characterization, spanning in silico, in vitro and in cell approaches. With increasing interest from pharmaceutical sectors, peptidomimetics hold promise for revolutionizing therapeutic approaches, marking a new era of precision drug discovery.