Concentration-Dependent Structural Transitions of Human Telomeric DNA Sequences

Abstract

Oligodeoxyribonucleotides (ODNs) that have four repeats of the human telomeric sequence d(TTAGGG)n can assume multiple monomolecular G-quadruplex topologies. These are determined by the cation species present, the bases at the 5′ or 3′ end, and the sample preparation technique. In this work, we report our studies of the concentration dependence of the circular dichroism (CD) and the vibrational modes probed by Raman scattering of three previously characterized monomolecular G-quadruplexes: H-Tel, d[5′-A(GGGTTA)3GGG-3′]; hybrid-1, d[5′-AAA(GGGTTA)3GGGAA-3′]; and hybrid-2, d[5′-TTA(GGGTTA)3GGGTT-3′]. At high (millimolar) ODN concentrations, we observed a transformation of the CD spectrum of H-Tel, with a relaxation time on the order of 10 h. Analysis of the kinetics of this process is consistent with the formation of an aggregated complex of folded H-Tel monomers. Upon dilution, the aggregates dissociate rapidly, yielding spectra identical to those of monomeric H-Tel. Both hybrid sequences undergo a similar...