X-pep, a novel cell-penetrating peptide motif derived from the hepatitis B virus

Montrose, Kristopher; Yang, Yi; Krissansen, Geoffrey W.

doi:10.1016/j.bbrc.2014.09.057

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Moreover, the truncated form of this X-pep peptide (Met-Ala-Ala-Arg-Leu amino acids (MAARL) sequence) was able to readily penetrate into hepatoblastoma G2 (HepG2) cells. Further truncation by removal of the terminal leucine amino acid reduced the cell-penetrating activity of this peptide, indicating that the MAARL sequence is the active core of this peptide [ 37 ].…”

Section: Why Cell Penetrating Peptides Are Of Particular Interest mentioning

confidence: 99%

Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway

et al. 2018

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Alternative therapeutic approaches against chronic hepatitis B virus (HBV) infection need to be urgently developed because current therapies are only virostatic. In this context, cell penetration peptides (CPPs) and their Peptide Nucleic Acids (PNAs) cargoes appear as a promising novel class of biologically active compounds. In this review we summarize different in vitro and in vivo studies, exploring the potential of CPPs as vehicles for intracellular delivery of PNAs targeting hepadnaviral replication. Thus, studies conducted in the duck HBV (DHBV) infection model showed that conjugation of (D-Arg)8 CPP to PNA targeting viral epsilon (ε) were able to efficiently inhibit viral replication in vivo following intravenous administration to ducklings. Unexpectedly, some CPPs, (D-Arg)8 and Decanoyl-(D-Arg)8, alone displayed potent antiviral effect, altering late stages of DHBV and HBV morphogenesis. Such antiviral effects of CPPs may affect the sequence-specificity of CPP-PNA conjugates. By contrast, PNA conjugated to (D-Lys)4 inhibited hepadnaviral replication without compromising sequence specificity. Interestingly, Lactose-modified CPP mediated the delivery of anti-HBV PNA to human hepatoma cells HepaRG, thus improving its antiviral activity. In light of these promising data, we believe that future studies will open new perspectives for translation of CPPs and CPP-PNA based technology to therapy of chronic hepatitis B.

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Section: Why Cell Penetrating Peptides Are Of Particular Interest mentioning

confidence: 99%

Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway

et al. 2018

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“…Another novel drug delivery platform with its groundwork on a CPP motif called X-Pep, derived from the extreme N -terminal region of the X-protein of HBV, is said to be applicable in having drugs delivered straight to cells specifically [ 96 ]. Researchers in another study also coinjected an N -acetylgalactosamine-melittin-like peptide (NAG-MLP) with a siRNA compounded to cholesterol that is directed to coagulation factor 7, and validated the oppression of HBV RNA, DNA, and proteins with a lengthy effective continuity.…”

Section: Novel Drug Delivery Strategies For Anti-hbv Therapeuticsmentioning

confidence: 99%

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

Singh

Indermun

Govender

et al. 2018

Viruses

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Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles. This review encompasses the strategies and techniques that have been utilized to target the HBV-infected nuclei in liver hepatocytes, with a significant look at the new insights and most recent advances in drug carriers and their role in anti-HBV therapy.

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“…form, suggesting the requirement of a stereoselective interaction with a chiral receptor to trigger cell entry [97]. In a recent study with a transferrin receptor specific CPP that crosses the BBB, modifications However, only the RI version was able to duplicate the permeability in a BBB model, showing that RI peptide reached an optimal balance between stability and potency, which is mediated by the right topological recognition by the transferrin receptor [98].…”

Section: Stereochemical Modificationmentioning

confidence: 99%

Strategies to Stabilize Cell Penetrating Peptides forIn VivoApplications

2015

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In the era of biomedicines and engineered carrier systems, cell penetrating peptides (CPPs) have been established as a promising tool for therapeutic application. Likewise, other therapeutic peptides, successful in vivo application of CPPs will strongly depend on peptide stability, the bottleneck for this type of biodegradable molecules. In this review, the authors describe the current knowledge of the in vivo degradation for known CPPs and the different strategies available to provide a higher resistance to metabolic degradation while preserving cell penetration efficiency. Peptide stability can be improved by different means, either modifying the structure to make it unrecognizable to proteases, or preventing access of proteolytic enzymes by applying conformation restriction or shielding strategies.

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X-pep, a novel cell-penetrating peptide motif derived from the hepatitis B virus

Cited by 11 publications

References 20 publications

Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway

Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

Strategies to Stabilize Cell Penetrating Peptides forIn VivoApplications

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