Design of Carrier Peptide-Oligonucleotide Conjugates with Rapid Membrane Translocation and Nuclear Localization Properties

Chaloin, Laurent; Vidal, Pierre; Lory, Philippe; Méry, Jean; Lautrédou, Nicole; Divita, Gilles; Heitz, Fréderic

doi:10.1006/bbrc.1997.8050

Cited by 96 publications

(64 citation statements)

References 31 publications

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“…More complicated conjugates have been devised to circumvent the problem of cellular uptake, for example NLS conjugates with lipophilic membrane-anchoring peptide domains or gold clusters. [29,30] Herein, we present the first example of the directed nuclear delivery of an organometallic compound, namely the cobaltocenium cation, by conjugation to the NLS peptide. Most of the metallocene bioconjugates prepared to date contain ferrocene (Fc) as the organometallic moiety.…”

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confidence: 99%

A Cobaltocenium–Peptide Bioconjugate Shows Enhanced Cellular Uptake and Directed Nuclear Delivery

et al. 2005

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confidence: 99%

A Cobaltocenium–Peptide Bioconjugate Shows Enhanced Cellular Uptake and Directed Nuclear Delivery

et al. 2005

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“…[29] Um diesem Dilemma zu entgehen, sind kompliziertere Konstrukte eingesetzt worden, beispielsweise NLSKonjugate mit Goldclustern oder lipophilen Peptiddomänen mit Affinität für Zellmembranen. [30,29] Wir präsentieren in dieser Arbeit erstmals die Möglich-keit, Organometallverbindungen wie das Cobaltocenium-Ion durch Konjugation mit dem NLS-Peptid gezielt in den Zellkern zu befördern. Die weitaus meisten MetallocenBiokonjugate enthalten Ferrocen als Organometallverbindung.…”

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Ein Peptid‐Cobaltocenium‐Biokonjugat mit verbesserter Aufnahme in Zellen und Anreicherung im Zellkern

et al. 2005

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“…A chimeric peptide MPG consisting of a hydrophobic fusion domain derived from HIV gp41 and a hydrophilic nuclear localization signal derived from the SV40 T-antigen was constructed to have membrane translocation property (529,534). This peptide was conjugated to a PS-ODN via a disulfide bond and greatly increased the cellular uptake of the ODN (534).…”

Section: Conjugation With Cell Penetrating Peptidesmentioning

confidence: 99%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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Design of Carrier Peptide-Oligonucleotide Conjugates with Rapid Membrane Translocation and Nuclear Localization Properties

Cited by 96 publications

References 31 publications

A Cobaltocenium–Peptide Bioconjugate Shows Enhanced Cellular Uptake and Directed Nuclear Delivery

A Cobaltocenium–Peptide Bioconjugate Shows Enhanced Cellular Uptake and Directed Nuclear Delivery

Ein Peptid‐Cobaltocenium‐Biokonjugat mit verbesserter Aufnahme in Zellen und Anreicherung im Zellkern

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

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