Conformational consequences of the incorporation of arabinofuranosylcytidine in DNA

Abstract

The self-complementary octamers d(CGCTAGCG) and d(CGaCTAGCG) (aC, arabinofuranosylcytidine) were studied by means of NMR spectroscopy. It is shown that d(CGaCTAGCG), under suitable conditions of oligonucleotide concentration, ionic strength and temperature, exclusively adopts a hairpin structure. However, under the same experimental conditions (5 mM DNA, no added salt, 295 K) d(CCCTAGCG) mainly adopts a B-DNA-type duplex. At lower temperatures (G290 K) the hairpin form of d(CGaCTACCG) occurs in slow exchange with an intact B-DNA-type duplex. When the DNA concentration of d(CGCTAGCG) is dramatically reduced (GO.5 mM) the hairpin form becomes highly favoured at the expense of the dimer. Moreover, protonchemical-shift considerations indicate that the structural features of the hairpin structure of d(CGCTAGCG) mimic, in part, those of the modified octamer d(CGaCTAGCG), i.e. a loop comprising only the two central residues with the thymine located into the minor groove (Pieters, J. M. L., de Vroom, E., van Recently, we carried out an NMR and model-building study on the modified octamer d(CGaCTAGCG) at low DNA concentration, ionic strength and temperature (Pieters et al., unpublished results). Under these experimental conditions the DNA compound exclusively prefers to adopt a monomeric hairpin structure. It was demonstrated that this hairpin structure consists of a double-helical stem formed by two WatsonCrick-type dC . dG base pairs and one aC . dG base pair, which closes the loop formed by the two remaining residues (Fig. 2). The vertical base stacking is not propagated into the loop region; instead, the thymine swings into the minor groove.In order to obtain detailed information regarding the effect of incorporation of aC into the DNA strand upon the Correspondence to C .

Effects of Arabinosylcytosine-Substituted DNA on DNA/RNA Hybrid Stability and Transcription by T7 RNA Polymerase

“…In addition, the C2-OH of the arabinose sugar was seen to project into the major groove of the helix at a site that is normally quite hydrophobic. NMR studies (Pieters et al, 1989(Pieters et al, ,1990Schweitzer et al, 1994) are largely consistent with the crystallographic study but reached different conclusions about the arabinose sugar conformation.…”

Effect of Cytarabine on the NMR Structure of a Model Okazaki Fragment from the SV40 Genome

“…Previous Cytarabine Studies. The importance of cytarabine for the treatment of leukemia has resulted in a number of investigations aimed at detecting structural alterations in nucleic acids substituted with cytarabine ( − ). Monomeric cytarabine adopts a C2‘-endo sugar pucker in the crystalline state, the same sugar pucker adopted by aC20 of [ARAC] in the present investigation ().…”

Solution Structure of a DNA Dodecamer Containing the Anti-Neoplastic Agent Arabinosylcytosine: Combined Use of NMR, Restrained Molecular Dynamics, and Full Relaxation Matrix Refinement

“…In an early study, a coupling constant analysis by solution NMR on the araC mononucleoside demonstrated that the araC sugar adopted a conformation under neutral pH conditions that was 50% C2'-endo and 50% C3'-endo, similar to that for ribocytosine; furthermore, no evidence for the type of intramolecular hydrogen bonding observed in the X-ray structure of the mononucleoside was seen under neutral conditions in solution (Remin et al, 1976). Two more recent NMR studies have been carried out on the decamer [d(CG) (araC)d(TAGCG)] 2 (Pieters et al, 1989(Pieters et al, ,1990). In the first report, incorporation of araC was found to promote increased formation of a hairpin structure in which the central TA residues formed the loop of the hairpin (Pieters et al, 1989).…”

“…Two more recent NMR studies have been carried out on the decamer [d(CG) (araC)d(TAGCG)] 2 (Pieters et al, 1989(Pieters et al, ,1990). In the first report, incorporation of araC was found to promote increased formation of a hairpin structure in which the central TA residues formed the loop of the hairpin (Pieters et al, 1989). Some formation of the duplex was observed, however, and a qualitative analysis of the data indicated that this duplex was B-type in structure.…”