Structure and drug interactions of parallel-stranded DNA studied by infrared spectroscopy and fluorescence.
The infrared spectra of three different 25-mer parallel-stranded DNAs (ps-DNA) have been studied. We have used ps-DNAs containing either exclusively dA x dT base pairs or substitution with four dG x dC base pairs and have them compared with their antiparallel-stranded (aps) reference duplexes in a conventional B-DNA conformation. Significant differences have been found in the region of the thymine C = O stretching vibrations. The parallel-stranded duplexes showed characteristic marker bands for the C2 = O2 and C4 = O4 carbonyl stretching vibrations of thymine at 1685 cm-1 and 1668 cm-1, respectively, as compared to values of 1696 cm-1 and 1663 cm-1 for the antiparallel-stranded reference duplexes. The results confirm previous studies indicating that the secondary structure in parallel-stranded DNA is established by reversed Watson--Crick base pairing of dA x dT with hydrogen bonds between N6H...O2 and N1...HN3. The duplex structure of the ps-DNA is much more sensitive to dehydration than that of the aps-DNA. Interaction with three drugs known to bind in the minor groove of aps-DNA--netropsin, distamycin A and Hoechst 33258--induces shifts of the C = O stretching vibrations of ps-DNA even at low ratio of drug per DNA base pair. These results suggest a conformational change of the ps-DNA to optimize the DNA-drug interaction. As demonstrated by excimer fluorescence of strands labeled with pyrene at the 5'-end, the drugs induce dissociation of the ps-DNA duplex with subsequent formation of imperfectly matched aps-DNA to allow the more favorable drug binding to aps-DNA. Similarly, attempts to form a triple helix of the type d(T)n.d(A)n.d(T)n with ps-DNA failed and resulted in the dissociation of the ps-DNA duplex and reformation of a triple helix based upon an aps-DNA duplex core d(T)10.d(A)10.
Fritzsche
H
H
Institute of Molecular Biology, Friedrich Schiller University Jena, Germany.
Akhebat
A
A
Taillandier
E
E
Rippe
K
K
Jovin
T M
TM
D001482:Base Composition; D001483:Base Sequence; D006690:Bisbenzimidazole / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004214:Distamycins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009429:Netropsin / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013055:Spectrophotometry, Infrared
D004214:Distamycins; D009429:Netropsin; C030000:stallimycin; D004247:DNA; D006690:Bisbenzimidazole