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

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Abstract
We have performed solid-state 31P-19F REDOR nuclear magnetic resonance (NMR) experiments to monitor changes in minor groove width of the oligo- nucleotide 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 6 0.7 A ˚ , comparable to that found for similar A:T-rich DNAs. Binding of a single drug molecule is observed to cause a 2.4 A ˚ decrease in groove width. Subsequent addition of a second drug molecule results in a larger conforma- tional change, expanding this minor groove width to 13.6 A ˚ , 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 Ain DNA- drug complexes and provide the first example of a direct spectroscopic measurement of minor groove width in nucleic acids.