title: A peptide nucleic acid-neamine conjugate that targets and cleaves HIV-1 TAR RNA inhibits viral replication.
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.
authors.affiliation: Laboratoire de Chimie Bio-Organique, Département de Pharmacochimie Moléculaire, UMR 5063 CNRS/Université Joseph Fourier-Grenoble I, FR CNRS 2607, BP 138, 5 Avenue de Verdun, F-38243 Meylan, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Riguet
authors.forename: Snehlata
authors.initials: S
authors.lastname: Tripathi
authors.forename: Binay
authors.initials: B
authors.lastname: Chaubey
authors.forename: Jérôme
authors.initials: J
authors.lastname: Désiré
authors.forename: Virendra N
authors.initials: VN
authors.lastname: Pandey
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Décout
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005601:Framycetin; D016325:HIV Long Terminal Repeat / Q000187:drug effects / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: C492674:12-(3,5-diamino-2-O-(2,6-diamino-2,6-dideoxyglucopyranosyl)-6-hydroxycyclohexyloxy)-1,6-diaza-2,5-dioxododecanyl-TCCCAGGCTCAGATCT-carboxamide; D000617:Aminoglycosides; D019380:Anti-HIV Agents; D020135:Peptide Nucleic Acids; D012367:RNA, Viral; D005601:Framycetin; C488396:neamine; D054303:HIV Reverse Transcriptase