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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
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Published on: September 19, 2022

Cell-penetrating peptide exploited syndecans.

Tamás Letoha1, Anikó Keller-Pintér, Erzsébet Kusz

  • 1Biological Research Center of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary. tletoha@yahoo.com

Biochimica Et Biophysica Acta
|February 9, 2010
PubMed
Summary

Cell-penetrating peptides (CPPs) utilize syndecan-4 as a receptor for cellular entry, mediating transport via heparan sulfate interactions. This discovery challenges previous hypotheses and opens avenues for targeted delivery technologies.

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Area of Science:

  • Cell biology
  • Biochemistry
  • Drug delivery

Background:

  • Cell-penetrating peptides (CPPs) facilitate intracellular delivery but their uptake mechanisms remain unclear.
  • The role of specific cell surface receptors in CPP internalization has been a long-standing question.

Purpose of the Study:

  • To investigate the mechanism of cellular uptake for common cationic CPPs.
  • To identify potential cell surface receptors involved in CPP internalization.

Main Methods:

  • Quantitative uptake studies were performed using CPPs and cells expressing syndecan-4.
  • Mutational analyses of syndecan-4 and its heparan sulfate chains were conducted.
  • The involvement of Protein kinase C alpha was assessed.

Main Results:

  • Syndecan-4 was identified as a binding partner and mediator for the uptake of penetratin, octaarginine, and TAT.
  • CPPs bind to syndecan-4 through specific interactions with its heparan sulfate chains.
  • Protein kinase C alpha plays a significant role in the CPP uptake process.

Conclusions:

  • This study provides the first direct evidence for receptor-mediated uptake of cationic CPPs.
  • The findings challenge the previously proposed membrane penetration hypothesis for CPPs.
  • The results pave the way for developing syndecan-4 targeted CPP delivery systems.