8-Methyl-2'-deoxyguanosine incorporation into parallel DNA quadruplex structures

This paper concerns the CD and NMR structural studies of the quadruple helix arrangements adopted by three tailored oligodeoxyribonucleotide analogs, namely d(TGMeGGT), d(TGGMeGT) and d(TGGGMeT), where dGMe represents a 8-methyl-2'-deoxyguanosine residue. The results of this study clearly demonstrate that the effects of the incorporation of dGMe instead of a dG residue are strongly dependent upon the positioning of a single base replacement along the sequence. As such, d(TGMeGGT), d(TGGMeGT) have been found to form 4-fold sym. quadruplexes with all strands parallel and equiv. to each other, each more stable than their natural counterpart. NMR expts. clearly indicate that [d(TGMeGGT)]4 possesses a GMe-tetrad with all dGMe residues in a syn-glycosidic conformation while an anti-arrangement is apparent for the four dGMe of [d(TGGMeGT)]4. As the two complexes show a quite different CD behavior, a possible relationship between the presence of residues adopting syn-glycosidic conformations and CD profiles is briefly discussed. As far as d(TGGGMeT) is concerned, NMR data indicate that at 25°C it exists primarily as a single-strand conformation in equil. with minor amts. of a quadruplex structure.