Polymorphism of human telomeric quadruplex structure controlled by DNA concentration: a Raman study

DNAconcentrationhasbeenrecentlysuggestedtobe the reason why different arrangements are revealed for K+-stabilized human telomere quadruplexes by experimental methods requiring DNA concentrations differing by orders of magnitude. As Raman spectros-copy can be applied to DNA samples ranging from those accessible by absorption and CD spectr-oscopies up to extremely concentrated solutions, gels and even crystals; it has been used here to clarify polymorphism of a core human telomeric sequence G3(TTAG3)3 in the presence of K +and Na+ ions throughout wide range of DNA concentrations. We demonstrate that the K+-structure of G3(TTAG3)3 at low DNA concentration is close to the antiparallel fold of Na+-stabilized quadruplex. On the increase of G3(TTAG3)3 concentration, a gradual transition from antiparallel to intramolecular parallel arrangement was observed, but only for thermodynamically equilibrated K+-stabilized samples. The transition is synergically supported by increased K+ concentra-tion. However, even for extremely high G3(TTAG3)3 and K+concentrations, an intramolecular antiparallel quadruplex is spontaneously formed from desalted non-quadruplex single-strand after addition of K+ ions. Thermal destabilization or long dwell time are necessary to induce interquadruplex transition. On the contrary, Na+-stabilized G3(TTAG3)3 retains its antiparallel folding regardless of the extremely high DNA and/or Na+concentrations, thermal destabiliza-tion or annealing