Cell-penetrating peptides (CPPs), developed for more than 30 years, are still being extensively studied due to their excellent delivery performance. Compared with other vehicles, CPPs hold promise delivering different types of drugs. Here, we review the development process and summarize composition classification CPP-based systems, cellular uptake mechanisms, influencing factors, biological bar...

Though much is taken, much abides; and though We are not now that strength which in old days Moved earth and heaven; that which we are, we are; One equal temper of heroic hearts, Made weak by time and fate, but strong in will To strive, to seek, to find, and not to yield Uptake mechanism of novel cell-penetrating peptides derived from the Alzheimer's disease associated gamma-secretase complex I...

Cyclic peptides have great potential as therapeutic agents and research tools but are generally impermeable to the cell membrane. Fusion of cyclic peptides with a cyclic cell-penetrating peptide produces bicyclic peptides that are cell-permeable and retain the ability to recognize specific intracellular targets. Application of this strategy to protein tyrosine phosphatase 1B and a peptidyl-prol...

Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptid...

Cytosolic protein delivery remains elusive. The inability of most proteins to cross the cellular membrane is a huge hurdle. Here we explore unique photothermal properties gold nanorods (AuNRs) trigger cytosolic proteins. Both partners, and AuNRs, are modified with protease-resistant cell-penetrating peptide nuclear targeting induce internalization. Once internalized, spatiotemporal control rele...

We investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)(3)K cell-penetrating peptide to target possible essential genes (ligA, rpoA, rpoD, engA, tsf, and kdtA) in Salmonella enterica serovar Typhimurium and inhibit bacterial growth in vitro and in cell culture. All targeted PNA-based gene inhibition has shown great potency in gene expression inhibition i...

This review focuses on the structure and mode-of-action of the two-peptide (class-IIb) bacteriocins that consist of two different peptides whose genes are next to each other in the same operon. Optimal antibacterial activity requires the presence of both peptides in about equal amounts. The two peptides are synthesized as preforms that contain a 15-30 residue double-glycine-type N-terminal lead...

A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC(50) of r7-kla (3.54 +/- 0.11 micromol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within mi...