Seite - (000242) - in Biomedical Chemistry: Current Trends and Developments

more than 25% of Trp. This peptide has the ability to permeate bacterial membranes and, depending on its three dimensional shape, inhibits DNA synthesis by binding to its strand (Hsu, 2005). His-rich amphipathic cationic peptides are peptides with 25% of their amino acids represented by His. They show a global cationic amphipathic helical structure. They trigger microorganism membrane disruption when the peptide adopts an alignment parallel to the membrane surface. However, pore formation is not essential for their high antimicrobial activity (Mason, 2009). Clavinin (van Kan, 2002) and daptomycin (Jeu & Fung, 2004) are two studied members of this antimicrobial peptide class. Cell-penetrating Peptides: A Tool for Effective Delivery The hydrophobic nature of cellular membranes protects cells from an influx of exogenous molecules, including bioactive molecules such as peptides, proteins, and oligonucleotides. New strategies have been developed to overcome these aspects, as microinjection, electroporation, and liposome and viral-based vectors. However, these methods have various drawbacks, including low efficiency, high toxicity, low bioavailability and poor specificity. An alternative strategy to traverse the phospholipid bilayer of the cell membrane emerged from two unexpected findings. In 1988, the HIV TAT transactivating factor was discovered (Frankel & Pabo, 1988) and a few years later, the Drosophila Antennapedia transcription factor (later named penetratin) was also discovered. TAT and penetratin served as the foundation for the development of a new type of molecular vector able to promote the delivery of a variety of cargos: cell-penetrating peptides (CPPs). A vast number of interdisciplinary studies report numerous applications for CPPs in the delivery of various cargos such as nucleic acids, polymers, liposomes, nanoparticles and low molecular weight drugs. The main characteristics of CPPs are low cytotoxicity, the ability to be taken up by a variety of cell types, dose-dependent efficiency and no restriction with respect to the size or type of cargo (Heitz, 2009). With a broad sequence variety and large differences in terms of physical chemical properties, CPPs can be linear, cyclical, cationic, hydrophobic, hydrophilic, amphipathic, non-amphipathic, random coiled, α-helical or β-sheets.