New methylene-bridged hexopyranosyl nucleoside modified oligonucleotides (BHNA): synthesis and biochemical studies
2009 (English)In: ARKIVOC, ISSN 1424-6376, no Part 3, 171-U46 p.Article in journal (Refereed) Published
The hyper-constrained nucleoside, methylene-bridged hexopyranosyl nucleoside (BHNA) was incorporated into the antisnese oligonucleotides (AON), which show more preference for binding toward the complementary RNA (T-m loss by ca 5 degrees C) than that with the complementary DNA (T-m loss by 10 C), vis-a-vis corresponding native duplex. The origin of reduction of T-m of the duplexes formed by the BHNA incorporated AON and the complementary RNA or DNA was further investigated by thermal denaturation study with the single-mismatched DNA or RNA, CD spectroscopy, RNase H digestion study, as well as by molecular model building. These studies showed that the introduction of BHNA causes only a limited local conformational perturbation in the AON/RNA heteroduplex, whereas it affects the global conformation in the AON-DNA duplex. BHNA incorporated AONs also show improved stability in the human blood serum, which may prove to have some potential therapeutic application.
Place, publisher, year, edition, pages
2009. no Part 3, 171-U46 p.
Conformationally-constrained nucleotide, hexopyranosyl nucleotide, antisense oligonucleotides (AON), nuclease stability, molecular modeling
IdentifiersURN: urn:nbn:se:uu:diva-106718ISI: 000265191400014OAI: oai:DiVA.org:uu-106718DiVA: diva2:225938