A Peptide Nucleic Acid–Aminosugar Conjugate Targeting Transactivation Response Element of HIV-1 RNA Genome Shows a High Bioavailability in Human Cells and Strongly Inhibits Tat-Mediated Transactivation of HIV-1 Transcription

Das, Indrajit; Désiré, Jérôme; Manvar, Dinesh; Baussanne, Isabelle; Pandey, Virendra N.; Décout, Jean Luc

doi:10.1021/jm300253q

Cited by 31 publications

(36 citation statements)

References 93 publications

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“…The cellular uptake of naked PNA is negligible. Earlier, we showed that PNA conjugated with neamine or glucosamine is efficiently taken up by the cells without endosomal entrapment (15,20) . We conjugated 15-mer biotinylated PNAs with neamine at the N terminus and with biotin at the C terminus via a Lys residue (Fig.…”

Section: Sequence Specificity Of Pna-neamine Conjugate Targeted To Comentioning

confidence: 97%

Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

Upadhyay

Dixit

Manvar

et al. 2013

Molecular & Cellular Proteomics

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Hepatitis C virus (HCV) infection leading to chronic hepatitis is a major factor in the causation of liver cirrhosis, hepatocellular carcinoma, and liver failure. This process may involve the interplay of various host cell factors, as well as the interaction of these factors with viral RNA and proteins. We report a novel strategy using a sequencespecific biotinylated peptide nucleic acid ( The hepatitis C virus, a blood-borne pathogen that causes chronic hepatitis, is the primary reason for liver transplantation in the United States. HCV 1 preferentially replicates in liver tissue without any direct cytopathic effect and thus is able to maintain long term, persistent infection. More than 50% of HCV-infected patients do not respond to treatment; instead, the majority of patients develop chronic hepatitis C, which leads to progressive liver fibrosis, cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The hepatitis C virus is a positive single-stranded RNA virus of a 9.6-kb genome. After its entry into cells, the (ϩ) strand RNA first serves as a messenger RNA for the translation of viral proteins. Newly synthesized HCV replicase (NS5B) then copies the (ϩ) strand RNA genome into the (Ϫ) strand RNA, which serves as a template for the production of the viral genome. The conserved 5Ј-and 3Ј-nontranslated (5ЈNTR and 3ЈNTR) regions of the HCV genome have multiple regulatory elements that are essential for replication of HCV and translation of viral proteins. Although the 5ЈNTR of HCV contains the internal ribosomal entry site, which is required for capindependent translation of (ϩ) strand HCV RNA (1-4), it is also the 3Ј region of the (Ϫ) strand RNA, which functions as the initiation site for replication of the (ϩ) strand HCV RNA genome. The 3Ј regions of both (Ϫ) and (ϩ) strand HCV RNAs are highly structured and serve as the initiation sites for viral replication (5). Various cellular proteins have been shown to interact with 5ЈNTR of HCV RNA; these include La autoantigen (6) nuclear factors NF90, NF110, NF45, and RNA helicase A (7), as well as the polypyrimidine tract-binding protein (8 -10). Recently, we affinity-captured different cellular proteins interacting with HCV 3ЈNTR and identified them by LC/MS/ MS; some of these proteins were found to be essential for HCV replication as confirmed by siRNA (11).Another recent study using sequence-specific gene silencing of the RNAi screen has identified 26 human genes encoding proteins that physically interact with HCV RNA or protein and modulate HCV replication (12). A more direct approach would be to capture the replicating HCV RNA genome in situ under physiological conditions and then identify all the cellular From the §Department of Biochemistry and Molecular Biology and Centre for the Study of Emerging and Re-emerging Pathogens,

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Section: Sequence Specificity Of Pna-neamine Conjugate Targeted To Comentioning

confidence: 97%

Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

Upadhyay

Dixit

Manvar

et al. 2013

Molecular & Cellular Proteomics

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“…More recently, in T-cell lymphocytes, the conjugation of aminoglucosamine to a peptide nucleic acid (PNA) targeting HIV-1 TAR significantly improved the cellular uptake of the PNA (Das et al, 2012). In addition, the amino sugar conjugate reduced luciferase activity greater than naked PNA and scrambled PNA conjugate controls.…”

Section: Targeted Conjugatesmentioning

confidence: 99%

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Juliano

Xin

Carver

et al. 2014

Nucleic Acid Therapeutics

110

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One of the major constraints on the therapeutic use of oligonucleotides is inefficient delivery to their sites of action in the cytosol or nucleus. Recently it has become evident that the pathways of cellular uptake and intracellular trafficking of oligonucleotides can strongly influence their pharmacological actions. Here we provide background information on the basic processes of endocytosis and trafficking and then review recent literature on targeted delivery and subcellular trafficking of oligonucleotides in that context. A variety of approaches including molecular scale ligand-oligonucleotide conjugates, ligand-targeted nanocarriers, and the use of small molecules to enhance oligonucleotide effects are discussed.

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“…The conjugation of amino sugars to an aglycone improves the basicity [35], alters the pharmacological properties [2,36,37], and also alters the mechanism of action of parent compound [38,39]. Moreover, the inherent positive charge of the amino sugar also enhances the solubility and potential for ionic interactions under normal physiological conditions [40,41].…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of amino deoxy-sugar-conjugated flavonol glycosides by engineered Escherichia coli

Pandey

Parajuli

Chu

et al. 2015

Biochemical Engineering Journal

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A Peptide Nucleic Acid–Aminosugar Conjugate Targeting Transactivation Response Element of HIV-1 RNA Genome Shows a High Bioavailability in Human Cells and Strongly Inhibits Tat-Mediated Transactivation of HIV-1 Transcription

Cited by 31 publications

References 93 publications

Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Biosynthesis of amino deoxy-sugar-conjugated flavonol glycosides by engineered Escherichia coli

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