Synthesis and structural studies by nuclear magnetic resonance of dodecadeoxynucleotides containing O6-methylguanine, O6-ethylguanine and O4-methylthymine.

Self-complementary dodecadeoxynucleotides containing either one O6-methylguanine (O6-meGua), one O6-ethylguanine (O6-etGua) or one O4-methylthymine (O4-meT) have been synthesized. They form double-stranded DNA in solution. The structures of these DNA helices containing O6-meGua:cytosine (C), O6-meGua:thymine (T), O6-etGua:C and Gua:O4-meT base pairs have been investigated by nuclear magnetic resonance (NMR). All these modified bases stack into the helix with the normal anti-glycosidic torsion angle; only in the helix containing an O6-etGua:C base pair was there evidence of significant distortion of the DNA structure. NMR did not show a strong hydrogen bond between N1 of Gua and N3 of O4-meT in the Gua:O4-meT base pair, or between N1 of O6-meGua and N3 of T in the O6meGua:T base pair. This casts doubt on the previously accepted structures for O4-meT:Gua and O6-meGua:T mispairs.