title: Glucose conjugation of anti-HIV-1 oligonucleotides containing unmethylated CpG motifs reduces their immunostimulatory activity.
abstract: Antisense oligodeoxynucleotides (ODNs) are short synthetic DNA polymers complementary to a target RNA sequence. They are commonly designed to halt a biological event, such as translation or splicing. ODNs are potentially useful therapeutic agents for the treatment of different human diseases. Carbohydrate-ODN conjugates have been reported to improve the cell-specific delivery of ODNs through receptor mediated endocytosis. We tested the anti-HIV activity and biochemical properties of the 5'-end glucose-conjugated GEM 91 ODN targeting the initiation codon of the gag gene of HIV-1 RNA in cell-based assays. The conjugation of a glucose residue significantly reduces the immunostimulatory effect without diminishing its potent anti-HIV-1 activity. No significant effects were observed in either ODN stability in serum, in vitro degradation of antisense DNA-RNA hybrids by RNase H, cell toxicity, cellular uptake and ability to interfere with genomic HIV-1 dimerisation.
authors: Instituto de Parasitología y Biomedicina "López-Neyra" (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avd. del Conocimiento s/n, Armilla, 18016 Granada (Spain); Present address: Estación Experimental del Zaidín, (EEZ-CSIC), C/ Prof. Albareda, 1, 18008 Granada, (Spain).
authors: José A
authors: JA
authors: Reyes-Darias
authors: Francisco J
authors: FJ
authors: Sánchez-Luque
authors: Juan Carlos
authors: JC
authors: Morales
authors: Sonia
authors: S
authors: Pérez-Rentero
authors: Ramón
authors: R
authors: Eritja
authors: Alfredo
authors: A
authors: Berzal-Herranz
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D018899:CpG Islands; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology; D013873:Thionucleotides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C079996:GEM91; D005947:Glucose
keywords: HIV-1 inhibition; antiviral agents; glycoconjugates; immune response reduction; oligonucleotides