Ligand-induced formation of hoogsteen-paired parallel DNA.
BACKGROUND
Based on molecular modeling studies, a model has been proposed for intercalation of triple-helix-specific ligands (benzopyridoindole (BPI) derivatives) into triple helices, in which the intercalating compounds interact mainly with the Hoogsteen-paired strands of the triple helix. We set out to test this model experimentally using DNA duplexes capable of forming parallel Hoogsteen base-paired structures.


RESULTS
We have investigated the possible formation of a parallel DNA structure involving Hoogsteen hydrogen bonds by thermal denaturation, FTIR spectroscopy and gel-shift experiments. We show that BPI derivatives bind to Hoogsteen base-paired duplexes and stabilize them. The compounds induce a reorganization from a non-perfectly matched antiparallel Watson- Crick duplex into a perfectly matched parallel Hoogsteen-paired duplex.


CONCLUSIONS
These results suggest that preferential intercalation of BPI derivatives in triple helices is due to their ability to interact specifically with the Hoogsteen-paired bases. The results are consistent with a model proposed on the basis of molecular modeling studies using energy minimization, and they open a new field of investigations regarding the biological relevance of Hoogsteen base-pairing.
Escudé
C
C
Laboratoire de Biophysique, INSERM U201 CNRS URA481, Muséum National d'Histoire Naturelle, 43, rue Cuvier, 75231 Paris Cedex 05, France.
Mohammadi
S
S
Sun
J S
JS
Nguyen
C H
CH
Bisagni
E
E
Liquier
J
J
Taillandier
E
E
Garestier
T
T
Hélène
C
C
D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D017550:Spectroscopy, Fourier Transform Infrared
D008024:Ligands; D004247:DNA