title: Synthesis of aminoglycoside-3'-conjugates of 2'-O-methyl oligoribonucleotides and their invasion to a 19F labeled HIV-1 TAR model.
abstract: The potential of aminoglycosides to induce RNA-invasion has been demonstrated. For this purpose, aminoglycoside-3'-conjugates of 2'-O-methyl oligoribonucleotides have been synthesized entirely on a solid phase. The synthesis includes an automated oligonucleotide chain elongation to solid-supported neomycin, ribostamycin, and methyl neobiosamine, and a two-step deprotection/release of the solid-supported conjugate, which allows exploitation of a simple protecting group scheme. Conjugates have been targeted to a (19)F labeled HIV-1 TAR RNA model (Trans Activation Response element of HIV), which allows monitoring of the invasion by (19)F NMR spectroscopy. A remarkably enhanced invasion, compared to that resulting from the corresponding unmodified 2'-O-methyl oligoribonucleotide (5'-CAGGCUCA-3'), has been obtained by the neomycin conjugate. The increased affinity results from a cooperative binding of the neomycin moiety and hybridization, though the invasion may also follow a mechanism, in which the first molar equivalent of the conjugate induces hybridization of the second.
authors.affiliation: Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kiviniemi
authors.forename: Pasi
authors.initials: P
authors.lastname: Virta
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis / Q000737:chemistry*; D005461:Fluorine; D016325:HIV Long Terminal Repeat; D015497:HIV-1; D006801:Humans; D007554:Isotopes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D058990:Molecular Targeted Therapy; D009355:Neomycin; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000617:Aminoglycosides; D007554:Isotopes; D009843:Oligoribonucleotides; D005461:Fluorine; D009355:Neomycin