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Intercalation complex of proflavine with DNA: structure and dynamics by solid-state NMR
P Tang1, C L Juang, G S Harbison
1Department of Chemistry, State University of New York, Stony Brook 11794-3400.
Science (New York, N.Y.)
|July 6, 1990
Summary
Proflavine binding to DNA causes significant structural changes in the DNA
Area of Science:
- Molecular Biology
- Biophysics
- Structural Biology
Background:
- Proflavine is a known DNA intercalating agent.
- Understanding drug-DNA interactions is crucial for drug development.
- Solid-state NMR provides insights into molecular structures.
Purpose of the Study:
- To elucidate the structural complex of proflavine bound to fibrous native DNA.
- To investigate the effects of proflavine intercalation on DNA conformation.
Main Methods:
- High-resolution one- and two-dimensional solid-state nuclear magnetic resonance (NMR).
- Utilized carbon-13 labeled proflavine and natural abundance carbon-13 NMR for DNA.
- Phosphorus-31 NMR was employed to study phosphodiester group orientation.
Main Results:
- Proflavine intercalates with its aromatic ring plane perpendicular to the DNA fiber axis and is immobile.
- Proflavine binding does not alter deoxyribose ring puckering.
- Significant changes in phosphodiester orientation observed: some parallel, others perpendicular to the helix axis.
Conclusions:
- Proflavine binding induces specific conformational changes in DNA phosphodiester backbones.
- The observed phosphodiester tilting likely accommodates intercalation and DNA unwinding.
- Solid-state NMR is effective in characterizing drug-DNA complex structures.