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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskning

Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Organic Chemistry
Vol/bind65
Udgave nummer17
Sider (fra-til)5167-5176
ISSN0022-3263
DOI
StatusUdgivet - 2000
Udgivet eksterntJa

Fingeraftryk

Derivatives
DNA
Monomers
Carbohydrates
locked nucleic acid
Oxygen
Atoms

Citer dette

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title = "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",
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.",
author = "L. Kv{\ae}rn{\o} and R. Kumar and B.M. Dahl and C.E. Olsen and J. Wengel",
year = "2000",
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journal = "Journal of Organic Chemistry",
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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. / Kværnø, L.; Kumar, R.; Dahl, B.M.; Olsen, C.E.; Wengel, J.

I: Journal of Organic Chemistry, Bind 65, Nr. 17, 2000, s. 5167-5176.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskning

TY - JOUR

T1 - 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

AU - Kværnø, L.

AU - Kumar, R.

AU - Dahl, B.M.

AU - Olsen, C.E.

AU - Wengel, J.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

U2 - 10.1021/jo000275x

DO - 10.1021/jo000275x

M3 - Journal article

VL - 65

SP - 5167

EP - 5176

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 17

ER -