Palindromic peptide foldamers: a strategy for structural stability and cellular uptake

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Mid-sized peptide therapeutics have gained significant attention for their potential to overcome the limitations of small molecules and biologics. However, their clinical application is often hindered by poor stability and low cellular permeability. In this study, we designed a palindromic peptide foldamer composed of L-leucine and L-arginine residues to investigate its structural and functional properties. CD spectroscopy confirmed that the designed peptide adopts a stable α-helical conformation, even under denaturing conditions. Cellular uptake studies using LC-MS/MS and flow cytometry indicated efficient intracellular delivery, suggesting that the peptide's amphiphilic structure enhances membrane permeability. These findings provide valuable insights into the rational design of structurally stable and functionally enhanced peptide therapeutics.