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

Valentina Bagnacani, Valentina Franceschi, Michele Bassi, Michela Lomazzi, Gaetano Donofrio (), Francesco Sansone (), Alessandro Casnati () and Rocco Ungaro
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Valentina Bagnacani: Università degli Studi di Parma, Parco Area delle Scienze 17/a
Valentina Franceschi: Università degli Studi di Parma, Via del Taglio 6
Michele Bassi: Università degli Studi di Parma, Parco Area delle Scienze 17/a
Michela Lomazzi: Università degli Studi di Parma, Parco Area delle Scienze 17/a
Gaetano Donofrio: Università degli Studi di Parma, Via del Taglio 6
Francesco Sansone: Università degli Studi di Parma, Parco Area delle Scienze 17/a
Alessandro Casnati: Università degli Studi di Parma, Parco Area delle Scienze 17/a
Rocco Ungaro: Università degli Studi di Parma, Parco Area delle Scienze 17/a

Nature Communications, 2013, vol. 4, issue 1, 1-7

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2721

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