Synthesis of abasic LNA (Locked Nucleic Acid) and two seco-LNA derivatives and evaluation of their hybridization properties compared with their more flexible DNA counterparts

L. Kværnø, R. Kumar, B.M. Dahl, C.E. Olsen, J. Wengel

Research output: Contribution to journalJournal articleResearch

Abstract

To investigate the structural basis of the unique hybridization properties of LNA (locked nucleic acid) three novel LNA derivatives with modified carbohydrate parts were synthesized and evaluated with respect to duplex stabilities. The abasic LNA monomer (X(L), Figure 1) with the rigid carbohydrate moiety of LNA but no nucleobase attached showed no enhanced duplex stabilities compared to its more flexible abasic DNA counterpart (X, Figure 1). These results suggest that the exceptional hybridization properties of LNA primarily originate from improved intrastrand nucleobase stacking and not backbone preorganization. Two monocyclic seco-LNA derivatives, obtained by cleavage of the C1'-O4' bond of an LNA monomer or complete removal of the O4'-furanose oxygen atom (Z(L) and dZ(L), respectively, Figure 1), were compared to their acyclic DNA counterpart (Z, Figure 1). Even though they are more constrained than Z, the seco-LNA derivatives Z(L) and dZ(L) destabilize duplex formation even more than the flexible seco-DNA monomer Z.

Original languageEnglish
JournalJournal of Organic Chemistry
Volume65
Issue number17
Pages (from-to)5167-5176
ISSN0022-3263
DOIs
Publication statusPublished - 2000
Externally publishedYes

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