Influence of the Dabcyl group on the cellular uptake of cationic peptides: short oligoarginines as efficient cell-penetrating peptides

Ildikó Szabó (1) , Françoise Illien (2) , Levente E Dókus (1) , Mo’ath Yousef (1) , Zsuzsa Baranyai (1) , Szilvia Bősze (1) , Shoko Ise (3) , Kenichi Kawano (3) , Sandrine Sagan (2) , Shiroh Futaki (3) , Ferenc Hudecz (1) , Zoltán Bánóczi (1)

1 ELTE - Eötvös Loránd University
2 LBM UMR 7203 - Laboratoire des biomolécules
3 Kyoto University

Cell-penetrating peptides (CPPs) are promising delivery vehicles. These short peptides can transport wide range of cargos into cells, although their usage has often limitations. One of them is the endosomatic internalisation and thus the vesicular entrapment. Modifications which increases the direct delivery into the cytosol is highly researched area. Among the oligoarginines the longer ones (n > 6) show efficient internalisation and they are well-known members of CPPs. Herein, we describe the modification of tetra- and hexaarginine with (4–((4–(dimethylamino)phenyl)azo)benzoyl) (Dabcyl) group. This chromophore, which is often used in FRET system increased the internalisation of both peptides, and its effect was more outstanding in case of hexaarginine. The modified hexaarginine may enter into cells more effectively than octaarginine, and showed diffuse distribution besides vesicular transport already at low concentration. The attachment of Dabcyl group not only increases the cellular uptake of the cell-penetrating peptides but it may affect the mechanism of their internalisation. Their conjugates with antitumor drugs were studied on different cells and showed antitumor activity.

Mots clés: Cell-penetrating peptides; Oligoarginine; Cationic cell-penetrating peptides; Drug conjugates; Antitumor activity; Cell-penetrating peptides

Domaines: Sciences pharmaceutiques; Biologie cellulaire

Ildikó Szabó, Françoise Illien, Levente E Dókus, Mo’ath Yousef, Zsuzsa Baranyai, et al.. Influence of the Dabcyl group on the cellular uptake of cationic peptides: short oligoarginines as efficient cell-penetrating peptides. Amino Acids, In press, 53 (7), pp.1033-1049. ⟨10.1007/s00726-021-03003-w⟩. ⟨hal-03237148⟩