AI Article Synopsis
- AONs with aza-ENA (1), carbocyclic-LNA-T (2), and carbocyclic-ENA-T (3) show strong durability against nucleases.
- They can effectively trigger an RNase H response, closely resembling that of native versions.
- These modifications enhance the potential for therapeutic applications in gene regulation.
Article Abstract
AONs containing aza-ENA (1), 5-membered (2) and 6-membered (3) carbocyclic analogs of LNA (carbocyclic-LNA-T) and ENA (carbocyclic-ENA-T) are both nuclease resistant and capable of eliciting RNase H response, very similar to that of the native.
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Article Synopsis
- AONs with aza-ENA (1), carbocyclic-LNA-T (2), and carbocyclic-ENA-T (3) show strong durability against nucleases.
- They can effectively trigger an RNase H response, closely resembling that of native versions.
- These modifications enhance the potential for therapeutic applications in gene regulation.
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July 2007
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Two unusual reactions involving the 5-hexenyl or the 6-heptenyl radical cyclization of a distant double bond at C4' and the radical center at C2' of the ribofuranose ring of thymidine have been used as key steps to synthesize North-type conformationally constrained cis-fused bicyclic five-membered and six-membered carbocyclic analogues of LNA (carbocyclic-LNA-T) and ENA (carbocyclic-ENA-T) in high yields. Their structures have been confirmed unambiguously by long range 1H-13C NMR correlation (HMBC), TOCSY, COSY, and NOE experiments. The carbocyclic-LNA-T and carbocyclic-ENA-T were subsequently incorporated into the antisense oligonucleotides (AONs) to show that they enhance the Tm of the modified AON/RNA heteroduplexes by 3.
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