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| Main Authors: | , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2026
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| Online Access: | https://onlinelibrary.wiley.com/doi/10.1002/psc.70106 |
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Table of Contents:
- A Single Hydrophobic Residue Enhances the Uptake of Short Cationic Proline‐Rich Cell‐Penetrating Peptides Adeline Schmitt Helma Wennemers Journal of Peptide Science ABSTRACT Cationic cell‐penetrating peptides (CPPs) are a versatile platform for intracellular cargo delivery into mammalian cells but often suffer from low cellular uptake and endosomal entrapment. Here, we investigated the effect of a single cyclohexylalanine (Cha) residue at the termini of short, conformationally constrained cationic peptides composed of (4 S )‐guanidiniumproline (Gup). We show that this hydrophobic residue promotes internalization. Our studies also revealed that a hydrophobic residue positioned at the C‐terminus enhances cellular uptake more than when at the N‐terminus. Comparative studies at different temperatures are consistent with a major entry pathway via direct translocation across the plasma membrane. The findings are useful for the design of CPPs, particularly for enhancing the cellular translocation of otherwise weakly cell‐penetrating peptides. 10.1002/psc.70106 http://creativecommons.org/licenses/by/4.0/