Expanding the Topological Landscape by a G-Column Flip of a Parallel G-Quadruplex

Canonical G-quadruplexes can adopt a variety of different topologies depending on the arrangement of propeller, lateral, or diagonal loops connecting the four G-columns. A novel intramolecular G-quadruplex structure is derived through inversion of the last G-tract of a threelayered parallel fold, associated with the transition of a single propeller into a lateral loop. The resulting (3+1) hybrid fold features three syn.anti.anti.anti G-tetrads with a 3'-terminal all-syn G-column. Although the ability of forming a duplex stem-loop between G-tracts seems beneficial for a propellerto-lateral loop rearrangement, unmodified G-rich sequences resist folding into the new (3+1) topology. However, refolding can be driven by the incorporation of syn-favoring guanosine analogues into positions of the fourth G-stretch. The presented hybrid-type G-quadruplex structure as determined by NMR spectroscopy may provide for an additional scaffold in quadruplex-based technologies.

Automated summary

Canonical G-quadruplexes can have diverse topologies based on the arrangement of loops connecting the G-columns, with a novel intramolecular G-quadruplex structure resulting from a change in the last G-tract of a three-layered fold. The newly formed (3+1) hybrid fold may offer potential applications in quadruplex-based technologies.