Arginine clustering on calix[4]arene macrocycles for improved cell penetration and DNA delivery

Nat Commun. 2013:4:1721. doi: 10.1038/ncomms2721.

Abstract

Cell-penetrating peptides are widely used as molecular transporters for the internalization inside cells of various cargo, including proteins and nucleic acids. A special role is played by arginine-rich peptides and oligoarginines covalently linked or simply mixed with the cargo. Here we report cell-penetrating agents in which arginine units are clustered on a macrocyclic scaffold. Instead of using long peptides, four single arginine units were covalently attached to either the upper or lower rim of a calix[4]arene, kept in the cone conformation building a 'parallel' cyclic array. These new macrocyclic carriers show high efficiency in DNA delivery and transfection in a variety of cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism*
  • Calixarenes / metabolism*
  • Calixarenes / pharmacokinetics
  • DNA / administration & dosage*
  • Humans
  • Macrocyclic Compounds / metabolism*
  • Macrocyclic Compounds / pharmacokinetics
  • Phenols / metabolism*
  • Phenols / pharmacokinetics
  • Transfection

Substances

  • Macrocyclic Compounds
  • Phenols
  • calix(4)arene
  • Calixarenes
  • DNA
  • Arginine