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Cell Penetrating Peptides

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Background

Cell Penetrating Peptides (CPPs) are a family of short, highly hydrophobic peptides with the function of penetrating cell membranes. CPPs are positively charged with the structure of less than 30 amino acids. Currently, CPPs are mainly applied to deliver bioactive substances such as oligopeptides, proteins, nucleotides or analogs, opening up new pathways for drug transcellular transport and providing new perspectives for improvement of drug delivery.

Classification

According to the amino acid composition, CPPs are classified into cationic and amphiphilic. Cationic CPPs are mainly rich in arginine and lysine, as representatives of nuclear transcription activator Tat protein derived peptide (YGRKKRRQRRR), Small molecule oligoarginine [(R) n] and small-molecule oligo-lysine [(K) n], etc. Except for oligo-lysine [(K) n], cationic CPPs contain at least one arginine residue. Amphiphilic CPPs are composed mainly of lysine, with other amino acid residues in hydrophilic or hydrophobic sequences, and exhibit an α-helical spatial conformation.

Applications in the delivery of bioactive substances

Although biomacromolecules are capable of modulating cell functions and exerting therapeutic effects, their large size as well as their negative electrical properties limit their therapeutic effects in vivo. Cross-linking of CCPs with small molecules such as paclitaxel, cyclosporine A and methotrexate empower their transcellular delivery and therefore, aggregated in the targeted tumor cells. One application for peptide and protein-based delivery is the cross-linking of TAT-penetrating peptides with transcription factor inhibitory peptides relevant to allergic diseases, which can reduce the inflammatory response of the body and therefore be used to treat allergic rhinitis and allergic asthma. Therapeutic nucleotides are highly hydrophilic and negatively charged, with minimal cellular uptake, and when CPPs and nucleotides bind non-covalently to form nanocomplexes the remodel nucleotides show improved cellular uptake.

Applications in bioimaging

The use of CCPs can enhance the penetration of reference agents and biosensors in organisms, such as enabling reference agents to cross the blood-brain barrier to detect fluorescence bio-signals in brain tissue, allowing radio-labeled antibodies to enter cells for radiation immunotherapy and radiation immunoassay, moreover, observing the process of virus infection of cells as well as propagation of virus particles between cells in real time.

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