Molecular Transporters: Synthesis of Oligoguanidinium Transporters and Their Application to Drug Delivery and Real‐Time Imaging

Abstract

Crossing borders. Methods to enhance or control selective passage of therapeutics or probes into or through biological barriers are a key to the future of drug therapy and many fundamental advances in science. One bioinspired strategy for crossing biological barriers is based on the use of molecular transporters, the focus of this minireview and our studies Stanford.

Disulfide crosslinked stearoyl carrier peptides containing arginine and histidine enhance siRNA uptake and gene silencing

“…The Tat peptide is rich in arginine residues and has six arginine residues and two lysine residues in the 13-amino-acid residue stretch. It has been shown that arginine residues play a critical role in intracellular uptake (Wender et al, 2000;Futaki et al, 2001a,b;Wadia et al, 2005;Goun et al, 2006). It has been reported that the interaction of arginine-rich peptides with membrane-associated proteoglycans results in activation of Rac, leading to F-actin reorganization and macropinocytosis .…”

A Novel, Bio-Reducible Gene Vector Containing Arginine and Histidine Enhances Gene Transfection and Expression of Plasmid DNA

“…[14][15][16] It has been reported that the interaction of arginine-rich peptides with membrane-associated proteoglycans results in activation of Rac, leading to F-actin reorganization and macropinocytosis. 17) Specifically, the guanidine group in arginine interacts with the carbonate, sulfate, and phosphate of the proteoglycans on the cellular surface and serves as intracellular delivery carriers of peptides, nucleotides, and even nanoparticles like liposomes and polymer micelles.…”

Cell penetrating peptides: overview and applications to the delivery of oligonucleotides

“…Tat Tumor associated proteins and peptides [81] Nucleic acids Tat Gene markers encapsulated in k phage [82] Various CPP Potential for CPP to deliver DNA [83] Imaging agents CPP for in vivo molecular imaging applications [84] Tat Paramagnetic labels [85] Tat Technetium and rhenium [86] Nanocarriers Tat Pharmaceutical nanocarriers [87] Solid lipid nanoparticles [88] Gold nanoparticles [89] Polymeric micelles [90] Liposomes Tat Tat Von Hippel Linau tumor suppressor peptide [99] Aside from nucleic acid-and peptide-based biomolecules, CPPs have improved the pharmacological properties of several low molecular weight drugs. For example, oligoArg conjugates of cyclosporine A were shown to be transported across the striatum corneum and to foster a local anti-inflammatory response upon topical application, thus providing a more selective effect than oral administration [22]. In the anti-tumoral drug field, CPP conjugation of Taxol was found beneficial in increasing the aqueous solubility of the drug and, importantly, overcoming multidrug resistance which is a frequent cause of resistance in cancer therapeutics [23].…”

“…Our own preliminary Ala scan on Tat 48-60 pointed to the important role of arginine residues in cell uptake [69]. Extensive structure function studies on the Tat peptides convincingly established the key role played by the guanidinium head groups of arginine in cell uptake and gave rise to oligoArg CPPs and to oligoguanidine peptoid derivatives [22]. These guanidinium groups are known to form bidentate hydrogen bonds with anions such as sulfates or phosphate groups.…”