IONIC CHANNELS FORMED BY A PRIMARY AMPHIPATHIC PEPTIDE-CONTAINING A SIGNAL PEPTIDE AND A NUCLEAR-LOCALIZATION SEQUENCE

The peptide SP-NLS Gly-Ala-Lys-Lys-Lys-Arg(20)-Lys-Val-NH-CH2-CH2-SH) is composed of a hydrophobic signal sequence (SP, Met-1 to Ala-16) fol lowed by a polycationic nuclear localization sequence (NLS, Lys-17 to Val-22) terminated by a cysteamide group. Designed to act as drug carr ier this primary amphipathic peptide proved cytotoxic and bactericidal when used at high concentrations, probably by inducing the formation of ion channels. In this work, we show that indeed SP-NLS exhibits a p ore-forming activity when incorporated into planar lipid bilayers and Xenopus laevis oocyte plasma membranes, with conductance values of 25 pS in 0.1 M NaCl. In both membranes, the insertion of the peptide was voltage-triggered whereas the induced conductances proved almost volta ge-independent. Moreover, SP-NLS ion channels were selective for monov alent cations (K+ > Na+ > Li+ > tetraethylammonium(+) > choline(+)). T he ion channel activity of this type of peptides thus provides some in sight on their toxicity but also on the mechanism involved for their m embrane crossing process. (C) 1998 Elsevier Science B.V. All rights re served.