Structure and drug interactions of parallel-stranded DNA studied by infrered spectroscopy and fluorescence

Overview of Fritzsche H. et al.

AuthorsFritzsche H., Akhebat A., Taillandier E., Rippe K., Jovin T.M.
AffiliationInstitute of Molecular Biology, Friedrich Schiller University Jena, Postfach 100813, D-07708 Jena, Germany, Laboratoire de Chimie Structurale et Spectroscopie Biomoleculaire, UFR de Medecine, Santé et Biologie Humaine, University Paris-Nord, F93012 Bobigny, France, Max-Planck Institute for Biophysical Chemistry, Postfach 2841, D-37018 Göttingen, Germny  
JournalNucleic Acids Research
Year 1993

Abstract


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.dT base pairs or substitution with four dG-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-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.