Bottom-Up Engineering of Peptide Cell Translocators Based on Environmentally Modulated Quadrupole Switches

Designing water-soluble peptides that camouflage their polarity to cross an anhydrous phase may significantly impact drug delivery. We engineered neutrally charged peptides endowed with a conformational switch that enables them to solubilize in both water and lipid. These peptides are capable of translocating without resorting to active internalization mechanisms. Lipid solubility is induced by a quadrupolar arrangement. Our passive translocation motif possesses the highest efficiency and is derived from cellular prions.