NMR-STUDY OF PARALLEL-STRANDED TETRAPLEX FORMATION BY THE HEXADEOXYNUCLEOTIDE D(TG4T)

MULTISTRANDED DNA structures based upon guanine association have been proposed to be important in the structure of chromosome telomeres1 and in immunoglobulin class switching2. Nucleic acids containing runs of guanine bases form a number of structures in vitro3-6, including fold-back structures (Fig. 1a)7-9 and parallel-stranded quadruplex structures in DNA2,10 and RNA11. The features of fold-back structures have now been determined at high-resolution12-14. The different structures are probably based on a tetrad of hydrogen-bonded guanine bases (Fig. 1b), with buffer conditions and sequence effects mediating isomerization between the different forms4,15-18. Here we use NMR spectroscopy to investigate the solution structure of the complex formed by the hexadeoxynucleotide d(TG4T) in the presence of sodium ions. We have observed the formation of a parallel-stranded quadruplex containing hydrogen-bonded tetrads of guanine. The parallel-stranded form differs significantly from the fold-back form, with individual nucleotide conformations being closer to those of B-form DNA.