Oligonucleotides incorporating N7-(2'-deoxy-beta-D-erythro-pentofuranosyl)isoguanine.

Article abstract of DOI:10.1081/NCN-120022844

The H-phosphonate and the phosphoramidite of N7-2'-deoxyisoguanosine (2) were prepared and incorporated into oligonucleotide duplexes. Their base pairing properties were investigated and compared with those of the parent purine nucleosides.

Full text of DOI:10.1081/NCN-120022844

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Oligonucleotides Incorporating N7-(2′-Deoxy-β-d-
erythro-pentofuranosyl)isoguanine
P. Leonard a , R. Kröschel a & F. Seela a b
a Laboratorium für Organische und Bioorganische Chemie , Institut für Chemie, Universität
Osnabrück , Osnabrück, Germany
b Organische Chemie und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück ,
Barbarastrasse 7, Osnabrück, D-49069, Germany
Published online: 31 Aug 2006.
To cite this article: P. Leonard , R. Kröschel & F. Seela (2003) Oligonucleotides Incorporating N7-(2′-Deoxy-β-d-erythro-
pentofuranosyl)isoguanine, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8, 1235-1237, DOI: 10.1081/NCN-120022844
To link to this article: http://dx.doi.org/10.1081/NCN-120022844
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 1235–1237, 2003
Oligonucleotides Incorporating N7-(20-Deoxy-b-D-
erythro-pentofuranosyl)isoguanine
*
¨
P. Leonard, R. Kroschel, and F. Seela
Laboratorium fur Organische und Bioorganische Chemie
¨
Institut fur Chemie, Universita¨t Osnabruck,
¨
¨
Osnabruck, Germany
¨
ABSTRACT
The H-phosphonate and the phosphoramidite of N7-20-deoxyisoguanosine (2)
were prepared and incorporated into oligonucleotide duplexes. Their base pairing
properties were investigated and compared with those of the parent purine
nucleosides.
Oligonucleotides incorporating 20-deoxyisoguanosine (1a) and its 7-deaza
derivatives 1b,c as well as the N7-glycosylated adenine or guanine form stable dup-
lex structures with parallel and antiparallel chain orientation.[1a–c] Now, the
N7-(20-deoxy-b-D-erythro-pento-furanosyl) isoguanine (2) was studied. The phos-
phoramidite 3 was prepared and employed in solid-phase oligonucleotide synthesis.
Apart from this corresponding N7- nucleosides such as the methylthio derivative 4
were synthesized.
*Correspondence: F. Seela, Organische Chemie und Bioorganische Chemie, Institut fur
¨
¨
Chemie, Universita¨t Osnabruck, Barbarastrasse 7, D-49069 Osnabruck, Germany; Fax:
¨
þ49 541 969 2370; E-mail: frank.seela@uni-osnabrueck.de.
1235
DOI: 10.1081/NCN-120022844
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

¨
Leonard, Kroschel, and Seela
1236
Earlier, the synthesis of 2 was reported by our laboratory.[2] Its H-phosphonate
was successfully employed in oligonucleotide synthesis. However, the application of
phosphoramidite chemistry failed. Thus, the 2-oxo function of 2 was protected with
the DPC-group (5 ! 6) and the dimethylaminomethylidene residue was used for
aminogroup protection. Compound 6 was converted into the DMT-derivative 7
and subsequently into the phosphoramidite 3.
Oligonucleotide duplexes containing 2 were prepared and hybridized with com-
plemen-tary strands incorporating dA, dC and dT (data not shown) or dG=5MeiCd
7
opposite to iGd.
From the Tm measurements it can be concluded, that only 20-deoxyguanosine
forms a strong base pair with 2. Nevertheless, the stability of this base pair depends
on the position of incorporation. It is not clear if this new base pair adopts a
Watson-Crick or a Hoogsteen-motif. As it is weaker than a dG-dC pair only two
hydrogen bonds are expected. As N7Gd forms strong triplex structures[3] similar
results can be expected for compound 2, also the formation of tetrameric structures
has to be considered.
7
Table 1. Tm-values of oligonucleotide duplexes containing iGd (2).a
Duplex
Tm [ꢀC]
51
Duplex
Tm [ꢀC]
36
50-d(TAGGTCAATACT)
30-d(ATCCAGTTATGA)
50-d(TAGGTGAATACT)
30-d(ATCCA7iGTTATGA)
50-d(TAG7iGACAATACT)
30-d(ATC G T GTTATGA)
44
50-d(TAGGT iCAATACT)b
30-d(ATCCA7iGTTATGA)
32
aMeasured in 1 M NaCl, 0.1 M MgCl2, 60 mM Na-cacodylate, pH 7.
bd(iC) ¼ 5-methyl-20-deoxyisocytidine.

N7-(20-Deoxy-b-D-erythro-pentofuranosyl)isoguanine
1237
REFERENCES
1. a) Seela, F.; Winter H. Bioorg. Med. Chem. Lett. 1993, 3, 273–276; b) Seela, F.;
Winter, H. Helv. Chim. Acta 1994, 77, 597–607; c) Seela, F.; Leonard, P. Helv.
Chim. Acta 1997, 80, 1301–1318.
2. Kazimierczuk, Z.; Mertens, R.; Kawczynski, W.; Seela, F. Helv. Chim. Acta
1991, 74, 1742–1748.
3. Brunar, H.; Dervan, P.B. Nucleic Acids Res. 1996, 24, 1987–1991.