Self-association of G-rich oligodeoxyribonucleotides under conditions promoting purine-motif triplex formation.
Efficient purine-motif triple-helix formation with guanosine/thymidine-rich oligodeoxyribonucleotides requires the presence of divalent cations (e.g., Mg2+) or polyamines at physiologic concentrations. However, under such conditions, we found that G-rich oligonucleotides were capable of self-association. Mixing experiments indicated a stoichiometry of two G-rich oligonucleotide strands in each complex. Dimerization was proportional to the oligonucleotide length, facilitated by increasing concentrations of multivalent cations, and inhibited by monovalent cations that promote G-quartet formation (e.g., K+, Rb+ NH4+). Although dimer formation was relatively slow (t(1/2) approximately 20 minutes), these species were quite stable, with dissociation rates on the order of days. Methylation protection experiments indicated that these dimers exhibited protected N7 position on most all guanines consistent with Hoogsteen base pairing, although this pattern differed from that observed under conditions favoring intramolecular quadruplex formation. Most important, G-rich oligonucleotide dimers were less capable of purine-motif triplex formation than were their denatured counterparts. Thus, these data indicated that G-rich oligodeoxyribonucleotides can form alternate self-associated structures under conditions that do not favor standard quadruplex formation and that these species can have altered properties with regard to their recognition of biologic targets.
Cheng
A J
AJ
Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Wang
J C
JC
Van Dyke
M W
MW
D001482:Base Composition; D002412:Cations / Q000378:metabolism; D019281:Dimerization; D006147:Guanine / Q000737:chemistry*; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry
D002412:Cations; D009838:Oligodeoxyribonucleotides; D006147:Guanine; D013941:Thymine