Design, synthesis and characterization of a new anionic cell-penetrating peptide: SAP(E).

Cell-penetrating peptides (CPPs) are powerful tools to transport cell-impermeable cargoes into the cytoplasm without damaging the cell membrane. The vast majority of these peptides described to date share several features, among others, they are positively charged at physiological pH. In several cases a clear correlation between an increasing number of positive charges and internalization properties has been reported. Here, we describe what, to the best of our knowledge, is the first anionic CPP. This new compound SAP(E) internalizes into a range of cell lines with good efficiency and it shows low toxicity. We also report on the internalization mechanism. The discovery of this new class of CPP opens the way to the intracellular delivery of new molecular cargoes.