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May 16, 2026RSC Chemical Biology0 citationsOpen Access

The Position of Hydrophobic Residues Impacts Cellular Uptake and Intracellular Localization of Cell Penetrating Peptides

ASAdeline SchmittHWHelma Wennemers

Key Points

  • This research aims to understand how the position of hydrophobic residues affects the uptake and localization of cell-penetrating peptides within cells.
  • Evaluated various hydrophobic residues in cell-penetrating peptides
  • Analyzed cellular uptake using mammalian cell models
  • Assessed intracellular localization and endosomal escape
  • Hydrophobic residues significantly improved cellular uptake and endosomal escape rates.
  • Specific positioning of these residues correlated with enhanced intracellular localization.
  • The study underscores the importance of peptide design in optimizing delivery.

Abstract

Cell-penetrating peptides (CPPs) are widely used to deliver cargo into mammalian cells, yet efficient cellular uptake and endosomal escape remain key challenges. In this study, we evaluated how hydrophobic (4S)-4-cyclohexylproline...

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Cite This Study

Schmitt et al. (2026) studied this question.

synapsesocial.com/papers/6a080969a487c87a6a40b5dbhttps://doi.org/10.1039/d6cb00107f
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Also Consider

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  1. 1Effects of cargo molecules on the cellular uptake of arginine-rich cell-penetrating peptides2005 · 249 citations
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  3. 3Effects of Terminal Functional Groups on the Stability of the Polyproline II Structure: A Combined Experimental and Theoretical Study2009 · 133 citations
  4. 4Hydrophobicity is a key determinant in the activity of arginine-rich cell penetrating peptides2022 · 53 citations
  5. 5Cytosolic Delivery of Proteins by Bioreversible Esterification2017 · 162 citations