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• W2252602787 endingPage "2019" @default.
• W2252602787 startingPage "2007" @default.
• W2252602787 abstract "Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson–Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson–Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2′-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context." @default.
• W2252602787 created "2016-06-24" @default.
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• W2252602787 date "2016-02-08" @default.
• W2252602787 modified "2023-10-06" @default.
• W2252602787 title "Next-generation bis-locked nucleic acids with stacking linker and 2′-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes" @default.
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• W2252602787 doi "https://doi.org/10.1093/nar/gkw021" @default.
• W2252602787 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4797291" @default.
• W2252602787 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26857548" @default.

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