Using solid-state 31P{19F} REDOR NMR to measure distances between a trifluoromethyl group and a phosphodiester in nucleic acids.

Abstract REDOR is a solid-state NMR technique frequently applied to biological structure problems. Through incorporation of phosphorothioate groups in the nucleic acid backbone and mono-fluorinated nucleotides, 31 P{ 19 F} REDOR has been used to study the binding of DNA to drugs and RNA to proteins through the detection of internuclear distances as large as 13–14 A. In this work, 31 P{ 19 F} REDOR is further refined for use in nucleic acids by the combined use of selective placement of phosphorothioate groups and the introduction of nucleotides containing trifluoromethyl (–CF 3 ) groups. To ascertain the REDOR-detectable distance limit between an unique phosphorous spin and a trifluoromethyl group and to assess interference from intermolecular couplings, a series of model compounds and DNA dodecamers were synthesized each containing a unique phosphorous label and trifluoromethyl group or a single 19 F nucleus. The dipolar coupling constants of the various 31 P and 19 F or –CF 3 containing compounds were compared using experimental and theoretical dephasing curves involving several models for intermolecular interactions.