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

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.