Molecular craftsmanship: reforging peptide backbones for enhanced drug design

In this review, peptide backbone modifications in drug design are analyzed, with fundamental principles and applications in pharmaceutical development being examined. A systematic classification of modification strategies is presented, including amide bond alterations, α-carbon modifications, backbone extensions, and conformational constraints. Synthetic methodologies, computational tools, and biological outcomes are evaluated, with particular emphasis placed on barriers to clinical translation. Current design paradigms are critically examined, and systematic biases along with unexpected effects are identified, while theoretical frameworks incorporating multi-scale phenomena are advanced. Limitations in computational modeling, regulatory considerations, and production challenges are addressed, and evidence-based solutions are proposed. Through the integration of chemical, biological, and computational perspectives, a foundation is provided for the advancement of peptide-based therapeutics.

• Zhang, P
• Hao, Y
• Xie, M
• Wang, H
• Gao, J

• Key BioAI Synthetica Lab for Natural Product Drug Discovery, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou 350002, China

• Request a Brochure
• Request more Info
• Request a Quote