Structural and Dynamic Properties of a Bromouracil-Adenine Base Pair in DNA Studied by Proton NMR

Abstract
We have synthesized and studied by proton NMR a duplex heptaoligonucleotide containing a 5-bromouracil (brU)—adenine base pair. This represents the first structural characterization of a B-form DNA containing brU. The brU·A base pair is Watson-Crick rather than Hoogsteen as seen for the monomers in the crystalline state. From analysis of the NOESY sepctra at very short mixing times evidence is presented that substitution of brU for T induces significant conformational changes from that of a normal B DNA The helix twist between brU4·Al1 and G3·C12 is ca.15° and for both brU4 and G3 the glycosyl torsion angles are significantly changed. The imino proton of the bru·A base pair shows a pH insensitive line width which shows that the pK of brU in this base pair is very much higher than that of the monomer.