8-Methyl-2'-deoxyguanosine incorporation into parallel DNA quadruplex structures (original) (raw)

2005, Nucleic Acids Research

This paper concerns the Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) structural studies of the quadruple helix arrangements adopted by three tailored oligodeoxyribonucleotide analogues, namely d(TG Me GGT), d(TGG Me GT) and d(TGGG Me T), where dG Me represents a 8-methyl-2 0deoxyguanosine residue. The results of this study clearly demonstrate that the effects of the incorporation of dG Me instead of a dG residue are strongly dependant upon the positioning of a single base replacement along the sequence. As such, d(TG Me GGT), d(TGG Me GT) have been found to form 4-fold symmetric quadruplexes with all strands parallel and equivalent to each other, each more stable than their natural counterpart. NMR experiments clearly indicate that [d(TG Me GGT)] 4 possesses a G Me-tetrad with all dG Me residues in a syn-glycosidic conformation while an anti-arrangement is apparent for the four dG Me of [d(TGG Me GT)] 4. As the two complexes show a quite different CD behaviour, a possible relationship between the presence of residues adopting syn-glycosidic conformations and CD profiles is briefly discussed. As far as d(TGGG Me T) is concerned, NMR data indicate that at 25 C it exists primarily as a single-strand conformation in equilibrium with minor amounts of a quadruplex structure.