Aryl-β-C-LNA monomers as universal hybridization probes

Article abstract of DOI:10.1081/NCN-120022955

High-affinity universal hybridization is demonstrated for oligonucleotides containing the pyrenyl-LNA monomer 6b, 2′-O-Me-RNA monomers and LNA monomers.

Full text of DOI:10.1081/NCN-120022955

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Aryl-β-C-LNA Monomers as Universal Hybridization
Probes
B. Ravindra Babu a & Jesper Wengel a b
a Nucleic Acid Center , Department of Chemistry , University of Southern Denmark , Odense
M, Denmark
b Nucleic Acids Center , Department of Chemistry , University of Southern Denmark ,
Campusvej 55, DK-5230, Odense M, Denmark
Published online: 31 Aug 2006.
To cite this article: B. Ravindra Babu & Jesper Wengel (2003) Aryl-β-C-LNA Monomers as Universal Hybridization Probes ,
Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 1317-1319, DOI: 10.1081/NCN-120022955
To link to this article: http://dx.doi.org/10.1081/NCN-120022955
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 1317–1319, 2003
Aryl-b-C-LNA Monomers as Universal
Hybridization Probes[1,2]
*
B. Ravindra Babu and Jesper Wengel
Nucleic Acid Center, Department of Chemistry, University of Southern
Denmark, Odense M, Denmark
ABSTRACT
High-affinity universal hybridization is demonstrated for oligonucleotides con-
taining the pyrenyl-LNA monomer 6b, 20-O-Me-RNA monomers and LNA
monomers.
Key Words: Universal bases; Universal hybridization; LNA, locked nucleic
acid.
Universal monomers that bind isoenergically with each of the natural nucleo-
tides include non-hydrogen bonding, hydrophobic nucleotides.[3] Although there
has been some success in the design of universal base analogues, examples that are
able to hybridize without significant duplex destabilization are rare. We decided to
synthesize the LNA[4] derivatives 6a and 6b, both based on the 20-O,40-C-methy-
lene-b-d-ribofuranosyl moiety known to be preorganized in a locked C30-endo
(N-type) RNA-like furanose conformation.
*Correspondence: Jesper Wengel, Nucleic Acids Center, Department of Chemistry, University
of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; Fax: þ45 66 15 8780;
E-mail: jwe@chem.sdu.dk.
1317
DOI: 10.1081/NCN-120022955
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1318
Babu and Wengel
Table 1. Thermal denaturation experiments (Tm values shown) for ON1-ON5 towards DNA
complements with each of the four natural bases in the central position.
DNA target:
30-d(CACTYTACG)
Y:
A
C
G
T
ON1
ON2
ON3
ON4
ON5
50-d(GTGATATGC)
28
12
18
35
39
11
5
17
14
38
12
6
18
19
37
19
7
19
21
40
50-d(GTGA6aATGC)
50-d(GTGA6bATGC)
50-d[20-OMe(GTGATATGC)]
50-d[20-OMe(GTLGA6bATLGC)]
Compared to the DNA reference ON1, introduction of the phenyl-LNA mono-
mer 6a (ON2) leads to reduced thermal stability of the resulting duplexes, and uni-
versal hybridization is not achieved due to the preferential binding to the target
DNA with the central adenine monomer (Table 1). The pyrene-LNA monomer 6b
(ON3) displays more encouraging properties, i.e., increased binding affinity com-
pared to 6a (ON2) and universal hybridization (the four Tm values ¼ 17–19ꢀC).
We then constructed ON5 as a mixture of six 20-O-Me-RNA monomers, one central
pyrenyl-LNA monomer 6b, and two affinity-enhancing LNA thymine monomers TL.
Indeed, the 2-O-Me-RNA=LNA chimera ON5 displays universal hybridization with
binding affinities exceeding those of the references ON1 and ON4 (the Tm values of
ON5 ¼ 37, 38, 39 and 40ꢀC).
The obtained results show that high-affinity universal hybridization can be
obtained by use of a combination of the pyrenyl-LNA monomer 6b, 20-O-Me-
RNA monomers and LNA monomers.
ACKNOWLEDGMENTS
The Danish National Research Foundation and The Danish Research Agency
are thanked for financial support.

Aryl-b-C-LNA Monomers
1319
REFERENCES
1. Babu, B.R.; Wengel, J. Universal hybridization using LNA (locked nucleic acid)
containing a novel pyrene LNA nucleotide monomer. Chem. Commun. 2001,
2114 pp.
2. Babu, B.R.; Prasad, A.K.; Trikha, S.; Thorup, N.; Parmar, V.S.; Wengel, J.
Conformationally locked aryl C-nucleosides: synthesis of phosphoramidite
monomers and incorporation into single-stranded DNA and LNA (locked
nucleic acid). J. Chem. Soc., Perkin Trans 1 2002, 2509 pp.
3. Loakes, D. The applications of universal DNA base analogues. Nucleic Acids
Res. 2001, 29, 2437 pp.
4. Wengel, J. Synthesis of 30-C- and 40-C-branched oligodeoxynucleotides and the
development of locked nucleic acid (LNA). Acc. Chem. Res. 1999, 32, 301 pp.