Matches in SemOpenAlex for { <https://semopenalex.org/work/W620826322> ?p ?o ?g. }
Showing items 1 to 55 of
55
with 100 items per page.
- W620826322 abstract "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 iH-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 3.5-5 °C and 1.5 °C/modification for carbocyclic-LNA-T and carbocyclic-ENA-T, respectively. Whereas the relative RNase H cleavage rates with carbocyclic-LNA-T, carbocyclic-ENA-T, aza-ENA-T, and LNA-T modified AON/RNA duplexes were found to be very similar to that of the native counterpart, irrespective of the type and the site modification in the AON strand, a single incorporation of carbocyclic-LNA and carbocyclic-ENA into AONs leads to very much more enhanced nuclease stability in the blood serum (stable >48 h) as compared to that of the native (fully degraded <3 h) and the LNA-modified AONs (fully degraded <9 h) and aza-ENA (≈85% stable in 48 h). Clearly, remarkably enhanced lifetimes of these carbocyclic-modified AONs in the blood serum may produce the highly desired pharmacokinetic properties because of their unique stability and consequently a net reduction of the required dosage. This unique quality as well as their efficient use as the AON in the RNase H-promoted cleavage of the target RNA makes our carbocyclic-LNA and carbocyclic-ENA modifications excellent candidates as potential antisense therapeutic agents." @default.
- W620826322 created "2016-06-24" @default.
- W620826322 creator A5066834061 @default.
- W620826322 date "2010-01-01" @default.
- W620826322 modified "2023-09-27" @default.
- W620826322 title "Carbon-Carbon Bond Formation via Radical Cyclization and Transition Metal Catalysis" @default.
- W620826322 hasPublicationYear "2010" @default.
- W620826322 type Work @default.
- W620826322 sameAs 620826322 @default.
- W620826322 citedByCount "0" @default.
- W620826322 crossrefType "journal-article" @default.
- W620826322 hasAuthorship W620826322A5066834061 @default.
- W620826322 hasConcept C104317684 @default.
- W620826322 hasConcept C10879258 @default.
- W620826322 hasConcept C129312508 @default.
- W620826322 hasConcept C185592680 @default.
- W620826322 hasConcept C24961977 @default.
- W620826322 hasConcept C552990157 @default.
- W620826322 hasConcept C55493867 @default.
- W620826322 hasConcept C67705224 @default.
- W620826322 hasConcept C69766542 @default.
- W620826322 hasConcept C71240020 @default.
- W620826322 hasConceptScore W620826322C104317684 @default.
- W620826322 hasConceptScore W620826322C10879258 @default.
- W620826322 hasConceptScore W620826322C129312508 @default.
- W620826322 hasConceptScore W620826322C185592680 @default.
- W620826322 hasConceptScore W620826322C24961977 @default.
- W620826322 hasConceptScore W620826322C552990157 @default.
- W620826322 hasConceptScore W620826322C55493867 @default.
- W620826322 hasConceptScore W620826322C67705224 @default.
- W620826322 hasConceptScore W620826322C69766542 @default.
- W620826322 hasConceptScore W620826322C71240020 @default.
- W620826322 hasLocation W6208263221 @default.
- W620826322 hasOpenAccess W620826322 @default.
- W620826322 hasPrimaryLocation W6208263221 @default.
- W620826322 hasRelatedWork W1968616635 @default.
- W620826322 hasRelatedWork W1992227890 @default.
- W620826322 hasRelatedWork W1998988517 @default.
- W620826322 hasRelatedWork W2000958467 @default.
- W620826322 hasRelatedWork W2011730629 @default.
- W620826322 hasRelatedWork W2012162678 @default.
- W620826322 hasRelatedWork W2012526468 @default.
- W620826322 hasRelatedWork W2021746684 @default.
- W620826322 hasRelatedWork W2024869506 @default.
- W620826322 hasRelatedWork W2028645657 @default.
- W620826322 hasRelatedWork W2079900893 @default.
- W620826322 hasRelatedWork W2089553631 @default.
- W620826322 hasRelatedWork W2137345081 @default.
- W620826322 hasRelatedWork W2147647211 @default.
- W620826322 hasRelatedWork W821066122 @default.
- W620826322 hasRelatedWork W901683742 @default.
- W620826322 isParatext "false" @default.
- W620826322 isRetracted "false" @default.
- W620826322 magId "620826322" @default.
- W620826322 workType "article" @default.