Cell Penetrating Peptides for Chemical Biological Studies

Significant progress has been made in the development of chemical biology methods used to study the molecular behavior and interplay among live cells. These include the development of novel fluorescent molecules and photo-cross-linking agents that can be used to determine the cellular locations of biomacromolecules (including proteins and nucleic acids). Various biosensors utilizing the remarkable ligand-recognition abilities of biomacromolecules have also been developed. To allow such chemically functionalized molecules to interact with their partners, and to fully exploit the abilities and functions thereof, it is necessary to efficiently deliver such molecules into cells, specifically into the cytosol. Here, we illustrate intracellular delivery methods employing arginine-rich cell-penetrating peptides (CPPs) (e.g., octa-arginine) in the presence of a counteranion, pyrenebutyrate. This approach is especially suitable for intracellular delivery of small proteins and peptides. Approaches employing arginine-rich CPPs tagged with a penetration-accelerating sequence can also be used toward this end.