Determination of DNA minor groove width in distamycin-DNA complexes by solid-state NMR

AUTOR(ES)

Olsen, Greg L.

FONTE

Oxford University Press

RESUMO

We have performed solid-state 31P-19F REDOR nuclear magnetic resonance (NMR) experiments to monitor changes in minor groove width of the oligonucleotide d(CGCAAA2′FUTGGC)·d(GCCAAT(pS)TT GCG) (A3T2) upon binding of the drug distamycin A at different stoichiometries. In the hydrated solid-state sample, the minor groove width for the unbound DNA, measured as the 2′FU7–pS19 inter-label distance, was 9.4 ± 0.7 Å, comparable to that found for similar A:T-rich DNAs. Binding of a single drug molecule is observed to cause a 2.4 Å decrease in groove width. Subsequent addition of a second drug molecule results in a larger conformational change, expanding this minor groove width to 13.6 Å, consistent with the results of a previous solution NMR study of the 2:1 complex. These 31P-19F REDOR results demonstrate the ability of solid-state NMR to measure distances of 7–14 Å in DNA–drug complexes and provide the first example of a direct spectroscopic measurement of minor groove width in nucleic acids.

Documentos Relacionados

• Conformational features of distamycin-DNA and netropsin-DNA complexes by Raman spectroscopy.
• High-resolution solid-state NMR of quadrupolar nuclei
• De novo determination of peptide structure with solid-state magic-angle spinning NMR spectroscopy
• Protein structural analysis from solid-state NMR-derived orientational constraints.
• Validation of the single-stranded channel conformation of gramicidin A by solid-state NMR