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

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• 作者：Indrajit Das ; J茅r么me D茅sir茅 ; Dinesh Manvar ; Isabelle Baussanne ; Virendra N. Pandey ; Jean-Luc D茅cout
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：July 12, 2012
• 年：2012
• 卷：55
• 期：13
• 页码：6021-6032
• 全文大小：469K
• 年卷期：v.55,no.13(July 12, 2012)
• ISSN：1520-4804

文摘

The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that the resulting PNA鈥揳minoglucosamine conjugate is stable under acidic conditions, efficiently taken up by the human cells and fairly distributed in both cytosol and nucleus without endosomal entrapment because cotreatment with endosome-disrupting agent had no effect on its cellular distribution. The conjugate displayed very high target specificity in vitro and strongly inhibited Tat mediated transactivation of HIV-1 LTR transcription in a cell culture system. The unique properties of this new class of PNA conjugate suggest it to be a potential candidate for therapeutic application.