Two-Repeat Human Telomeric d(TAGGGTTAGGGT) Sequence Forms Interconverting Parallel and Antiparallel G-Quadruplexes in Solution: Distinct Topologies, Thermodynamic Properties, and Folding/Unfolding Kinetics

We demonstrate by NMR that the two-repeat human telomeric sequence d(TAGGGTTAGGGT) can form both parallel and antiparallel G-quadruplex structures in K+-containing solution. Both structures are dimeric G-quadruplexes involving three stacked G-tetrads. The sequence d(TAGGGUTAGGGT), containing a single thymine-to-uracil substitution at position 6, formed a predominantly parallel dimeric G-quadruplex with double-chain-reversal loops; the structure was symmetric, and all guanines were anti. Another modified sequence, d(UAGGGTBrUAGGGT), formed a predominantly antiparallel dimeric G-quadruplex with edgewise loops; the structure was asymmetric with six syn guanines and six anti guanines. The two structures can coexist and interconvert in solution. For the latter sequence, the antiparallel form is more favorable at low temperatures (<50 °C), while the parallel form is more favorable at higher temperatures; at temperatures lower than 40 °C, the antiparallel G-quadruplex folds faster but unfolds slower than the parallel G-quadruplex.