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Synthesis of Aminoglycoside-3 '-Conjugates of 2 '-O-Methyl Oligoribonucleotides and Their Invasion to a F-19 labeled HIV-1 TAR Model
Tekijät: Kiviniemi A, Virta P
Kustantaja: AMER CHEMICAL SOC
Julkaisuvuosi: 2011
Journal: Bioconjugate Chemistry
Tietokannassa oleva lehden nimi: BIOCONJUGATE CHEMISTRY
Lehden akronyymi: BIOCONJUGATE CHEM
Vuosikerta: 22
Numero: 8
Aloitussivu: 1559
Lopetussivu: 1566
Sivujen määrä: 8
ISSN: 1043-1802
DOI: https://doi.org/10.1021/bc200101r
Tiivistelmä
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 F-19 labeled HIV-1 TAR RNA model (Trans Activation Response element of HIV), which allows monitoring of the invasion by F-19 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.
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 F-19 labeled HIV-1 TAR RNA model (Trans Activation Response element of HIV), which allows monitoring of the invasion by F-19 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.
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