DNA containing non-nucleosidic phenanthrene building blocks with asymmetrical linkers

Article abstract of DOI:10.1080/15257770701506319

The synthesis and hybridization properties of oligonucleotides containing phenanthrene building blocks with non-nucleosidic linkers of different length are described. It was found that the length of the linkers, as well as the combination of unequal linke

Full text of DOI:10.1080/15257770701506319

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DNA Containing Non-Nucleosidic
Phenanthrene Building Blocks with
Asymmetrical Linkers
Simon M. Langenegger a , Vladimir L. Malinovskii a , Daniel Wenger a
, Sarah Werder a & Robert Häner a
a Department of Chemistry and Biochemistry , University of Bern ,
Bern, Switzerland
Published online: 10 Dec 2007.
To cite this article: Simon M. Langenegger , Vladimir L. Malinovskii , Daniel Wenger , Sarah
Werder & Robert Häner (2007) DNA Containing Non-Nucleosidic Phenanthrene Building Blocks
with Asymmetrical Linkers, Nucleosides, Nucleotides and Nucleic Acids, 26:8-9, 901-903, DOI:
10.1080/15257770701506319
To link to this article: http://dx.doi.org/10.1080/15257770701506319
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Nucleosides, Nucleotides, and Nucleic Acids, 26:901–903, 2007
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770701506319
DNA CONTAINING NON-NUCLEOSIDIC PHENANTHRENE
BUILDING BLOCKS WITH ASYMMETRICAL LINKERS
Simon M. Langenegger, Vladimir L. Malinovskii, Daniel Wenger,
Sarah Werder, and Robert Ha¨ner
Department of Chemistry and Biochemistry,
2
University of Bern, Bern, Switzerland
The synthesis and hybridization properties of oligonucleotides containing phenanthrene build-
2
ing blocks with non-nucleosidic linkers of different length are described. It was found that the length
of the linkers, as well as the combination of unequal linkers can have a substantial influence on the
thermal stability of the modified DNA.
Keywords phenanthrene building blocks; non-nucleosidic linkers; thermal stability
Modified oligonucleotides have found widespread application as diagnos-
tic and research tools. Furthermore, due to the repetitive, well-defined
arrangement of their building blocks, nucleic acids, and related types of
oligomers are ideal objects for the designed construction of larger as-
semblies and architectures.[1−7] In previous work we showed that non-
nucleosidic phenanthrene building blocks with identical linkers on both
sides can be used as base surrogates leading to stable hybrids.[8,9] We have
now extended our studies to the investigation of hybrids containing non-
identical linkers. These data are described herein.
The synthesis of the phenanthrene-derived phosphoramidite building
blocks containing linkers of different lengths is shown in Scheme 1. The
preparation of the phenanthrene derivatives started from phenanthrene-
3,6-dicarboxylic acid (1), which had been prepared according to the
method described previously.[8,10] Derivatization with the corresponding
α,ω-aminoalcohols gave the amides 2a–d. Subsequent phosphitylation pro-
vided the phosphoramidites 3a–d. The phenanthrene-derived phospho-
ramidite building blocks 3a–d were subsequently incorporated into oligonu-
cleotides by standard oligonucleotide synthesis. Coupling yields with the
modified phosphoramidites were equal to the ones obtained with auto-
mated nucleoside building blocks. After deprotection (conc. ammonia,
Address correspondence to Robert Ha¨ner, Department of Chemistry and Biochemistry, University
of Bern, Freiestrasse 3, Bern CH 3012, Switzerland. E-mail: robert.haener@ioc.unibe.ch
901

902
S. M. Langenegger et al.
SCHEME 1 Synthesis of the phenanthrence-derived phosphoramidite building blocks.
55◦C), all oligomers were purified by reversed-phase HPLC and character-
ized by high-resolution mass spectrometry.
Thermal denaturation experiments revealed that all phenanthrene con-
taining oligonucleotides form a stable duplex. The data indicate that the
linker length is an important factor for the overlap of the phenanthrene
residues. A remarkable destabilisation results if the linker is too short for
TABLE 1 Influence of the replacement of natural base pairs by phenanthrene building blocks
containing different types of non-nucleosidic linkers on the thermal stability of duplex DNA
(Conditions: 100 mM NaCl, pH 7.4, 10 mM TrisHCl, 1 µM DNA duplex).
Entry
1
Duplex
Tm(◦C)
68.0
ꢀT(◦C)
5ꢁ AGC TCG GTC ATC GAG AGT GCA
3ꢁ TCG AGC CAG TAG CTC TCA CGT
5ꢁ AGC TCG GTC A2P2C GAG AGT GCA
3ꢁ TCG AGC CAG T2P2G CTC TCA CGT
5ꢁ AGC TCG GTC A4P4C GAG AGT GCA
3ꢁ TCG AGC CAG T4P4G CTC TCA CGT
5ꢁ AGC TCG GTC A2P2C GAG AGT GCA
3ꢁ TCG AGC CAG T4P4G CTC TCA CGT
5ꢁ AGC TCG GTC A4P4C GAG AGT GCA
3ꢁ TCG AGC CAG T2P2G CTC TCA CGT
5ꢁ AGC TCG GTC A2P4C GAG AGT GCA
3ꢁ TCG AGC CAG T2P4G CTC TCA CGT
5ꢁ AGC TCG GTC A4P2C GAG AGT GCA
3ꢁ TCG AGC CAG T4P2G CTC TCA CGT
5ꢁ AGC TCG GTC A2P4C GAG AGT GCA
3ꢁ TCG AGC CAG T4P2G CTC TCA CGT
5ꢁ AGC TCG GTC A4P2C GAG AGT GCA
3ꢁ TCG AGC CAG T2P4G CTC TCA CGT
2
3
4
5
6
7
8
9
62.3
67.3
66.3
60.0
66.2
68.0
68.0
69.3
−6.7
−0.7
−1.7
−8.0
−1.8
0.0
0.0
1.3
mPn

DNA Containing Non-Nucleosidic Phenanthrene
903
sufficient overlap of the phenanthrenes, (see Table 1, entries 2 and 3). If
phenanthrene building blocks with linkers of different length are placed in
opposite positions, a difference of 6.3◦C in the Tm (melting temperature) is
observed between the two different possibilities (see Table 1, entries 4 and
5). Thus, it seems that the interaction of the phenanthrene units with the
adjacent base pairs has a significant influence on the thermal stability of the
duplex.
Hybrids with asymmetrical phenanthrene building blocks (i.e., when the
two linkers on a particular phenanthrene are of different length) are gener-
ally well tolerated (Table 1, entries 6–9). The highest Tm value was observed
with the hybrid containing the building block 3c (see Scheme 1) in each
oligomer (Table 1, entry 9).
In conclusion, oligodeoxynucleotides containing 3,6-disubstituted
phenanthrenes with various combinations of non-nucleosidic linkers were
prepared and investigated. The thermal stability of the hybrids was found to
be influenced by the length of the linkers, as well as by the relative arrange-
ment of the different linkers. In addition, also the oligonucleotide sequence
is important for the stability of the respective hybrids.
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