The Novel Cell Penetrating Peptide NrTP Exquisitely Targets the Nucleolus of Tumor Cells

摘要

Localization sequences are specific signals that sort proteins to precise cellular compartments. Among those, cell-penetrating peptides (CPPs) are natural or synthetic sequences, cationic and amphipathic, capable of translocating eukaryotic membranes, occasionally localizing to the nucleus. Animal venoms, for their part, are a rich source of bioactive peptides that on occasion can be turned into useful drugs. Snakes, scorpions or spiders produce and secrete a valuable diversity of toxins capable of interacting with distinct molecular targets. A limited number of animal toxins is known to translocate the cytoplasmic membrane and localize into distinct cell compartments. One example is crotamine [1], a rattlesnake toxin of 42 amino acids that selectively translocates into cells at specific phases of cell cycle, and localizes to the nucleus. In solution, crotamine adopts an αβββ fold, stabilized by three disulfide bonds [2], similar to βdefensin 2 and Na~+-channel scorpion toxin.