细胞穿透肽的研究进展

chemical linkage of CPPs
chemical linkage of CPPs
Examples of covalent conjugation are neutral cargo (phosphorodiamidate morpholino oligomers (PMO), peptide nucleic acids (PNA), small drug molecules) complexes which can be coupled to CPPs via a disulfide bond, an amide bond, or other specific linkers. Noncovalent complexes are formed via electrostatic and/or hydrophobic interactions between negatively charged cargo molecules, such as nucleic acids (siRNA, pDNA, etc.),and a positively charged CPP. CPP-cargo complexes need to escape from the endosmal vesicles in order to induce a biological effect. Ways:One line of thinking is that hydrophobic and electrostatic interactions occur between the endosomal membrane and the nanoparticles, which leads to disruption of the endosomes. Another the proton sponge theory, proposes that endosomes burst due to osmotic pressure
chemical linkage of CPPs
Part4
CPPs transmembrane mechanism
Part5
CPPs Applications
Background
cell membrane
selectively permeable barrier
Cell-penetrating peptides (CPPs) fewer than 30 amino acids、enter cells、endocytosis、 conjugated bioactive cargos[1]
CPPs Applications
CPPs Applications
Properly developed CPPs and their conjugates with therapeutics offer a very promising pathway to deliver lower concentrations of toxic drugs to critical tissues such as tumors, heart, etc. Small chemotherapeutic drugs have also been delivered by CPPs (doxorubicin,methotrexate, cyclosporine A, paclitaxel).[8] Cao et al. produced a biologically active Bcl-xL fusion protein containing an 11 amino acid CPP from TAT protein and a hemagglutinin (HA) tag that allowed in vitro and in vivo delivery into neurons[9] Other fuction such as promoting intestinal absorption of insulin,New peptide for ocular tissue transport-POD and so on.
Amphipathic CPPs Amphiphilic cell-penetrating peptides are composed mainly of lysine 。 There are also distributed to other hydrophilic or hydrophobic amino acid residues in the sequence, which spatial conformation of α-helix structure 。 Amphoteric helix having hydrophilic and hydrophobic properties is necessary for the structure through the membrane 。such as pVEC 、ARF and proline-rich peptides。
CPPs classification
CPP sequences are known to vary considerably as seen by Table 1. Similarities:positively charged amino acids(R、K) The membranolytic properties:positively charge,secondary structure,specifically helicity
Reference
[1]D.M. Copolovici, K. Langel, E. Eriste, U. Langel, Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8 (2014) 1972-1994.
CPPs classification
Even though CPPs have a great sequence variety, it is possible to bbgroups defined by their physical– chemical properties: cationic, amphipathic and hydrophobic。[7]
Conclusion
cell-penetrating peptides can efficiently traverse the plasma membrane of both cells and tissues and are successfully used as delivery vectors for therapeutic molecules. Due to their positive charge, CPPs can be covalently conjugated to active biomolecules (nucleic acids, peptides,proteins, chemotherapeutic drugs, etc.). After efficient cellular internalization, CPPs are able to release their cargo into the cytosol in order to promote the desired biological effect. When coupled to a cargo, CPPs use endocytosis as the main cellular translocation mechanism.Prior to use, CPPs must undergo both pharmacological and toxicological studies in vivo. Considering evidence from numerous studies, CPPs have the potential to become a universal tool to carry therapeutic molecules across cellular membranes without a risk of toxicity or inflammatory reactions
Recent progress of cellpenetrating peptides as new carriers for intracellular cargo delivery
CONTENTS Contents
Part1
Background
Part2
CPPs classification
Part3
Cationic CPPs
Cationic peptides are a class of peptides with a high positive net charge and few acidic amino acid residues.Typical, the cationic CPPs are including R9 , Tat, hLF and (RXR)4 and so on.
CPPs
Advantages of CPPs CPPs application siRNA, nucleic acids, proteins、 Nanoparticles、 Chemotherapy drugs、 Liposomes[2-6]
Biological safety、 cellular uptake、 be designed 、 Low cytotoxicity
CPPs classification
Hydrophobic CPPs Peptides which contain only apolar residues are considered as hydrophobic peptides。So far, only a few hydrophobic CPP sequences have been discovered such as the signal sequences from integrin β3 (VTVLALGALAGVGVG) and Kaposi fibroblast growth factor (AAVALLPAVLLALLAP)