Abstract
The neamine part of the aminoglycoside antibiotic neomycin B was conjugated to a 16 mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. Attachment of the neamine core allows cellular uptake of the PNA and results in potent inhibition of HIV-1 replication. The polycationic neamine moiety imparts greater solubility to the PNA and also confers a unique RNA cleavage property to the conjugate which is specific to its target site and functional at physiological concentrations of Mg(2+). These properties suggest a potential therapeutic application for this class of compounds.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aminoglycosides / chemistry
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / metabolism
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Anti-HIV Agents / pharmacology*
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Binding Sites
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Biochemistry / methods
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Cells, Cultured
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Drug Evaluation, Preclinical / methods
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Framycetin
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HIV Long Terminal Repeat / drug effects
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HIV Long Terminal Repeat / genetics
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HIV Reverse Transcriptase / antagonists & inhibitors
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HIV Reverse Transcriptase / metabolism
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HIV-1 / drug effects*
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HIV-1 / genetics
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Humans
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Lymphocytes / drug effects
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Lymphocytes / virology
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Peptide Nucleic Acids / chemistry*
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Peptide Nucleic Acids / metabolism
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Peptide Nucleic Acids / pharmacology*
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RNA, Viral / drug effects
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Structure-Activity Relationship
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Virus Replication / drug effects
Substances
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12-(3,5-diamino-2-O-(2,6-diamino-2,6-dideoxyglucopyranosyl)-6-hydroxycyclohexyloxy)-1,6-diaza-2,5-dioxododecanyl-TCCCAGGCTCAGATCT-carboxamide
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Aminoglycosides
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Anti-HIV Agents
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Peptide Nucleic Acids
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RNA, Viral
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Framycetin
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neamine
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HIV Reverse Transcriptase