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

We have performed solid-state P-31-F-19 REDOR nuclear magnetic resonance (NMR) experiments to monitor changes in minor groove width of the oligonucleotide d(CGCAAA(2'F)UTGGC).d(GCCAAT(pS)TT GCG) (A(3)T(2)) 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'F)U7-pS19 inter-label distance, was 9.4 +/- 0.7 Angstrom, comparable to that found for similar A:T-rich DNAs. Binding of a single drug molecule is observed to cause a 2.4 Angstrom 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 Angstrom, consistent with the results of a previous solution NMR study of the 2:1 complex. These P-31-F-19 REDOR results demonstrate the ability of solid-state NMR to measure distances of 7-14 Angstrom in DNA-drug complexes and provide the first example of a direct spectroscopic measurement of minor groove width in nucleic acids.