Monomolecular tetrahelix of polyguanine with a strictly defined folding pattern

Abstract

The G3TG3TG3TG3 (G3T) sequence folds into a monomolecular quadruplex with all-parallel G3 segments connected to each other by chain-reversal loops. The homopolymer consisting of n number of G3T domains directly conjugated to each other folds into an uninterrupted and unusually stable polymer, tetrahelical monomolecular DNA (tmDNA). It was demonstrated that the tmDNA architecture has strong potential in nanotechnologies as highly programmable building material, high affinity coupler and the driving force for endergonic reactions. Here, we explore capability of analogous DNA sequences (i.e., monomolecular quadruplexes with G2 or G4 segments) to construct tmDNA architecture. The study demonstrates that tmDNA can have only one building pattern based on a quadruplex domain with three G-tetrads and single-nucleotide loops, G3N (N = G, A, C and T); all other domains demonstrate antiparallel topologies unsuitable for tmDNA. The present study also suggests that polyguanine is capable of tmDNA formation with strictly defined building pattern; G3 segments connected to each other by chain-reversal G-loops. These findings can have significant impact on (i) DNA nanotechnologies; (ii) structure prediction of G-rich sequences of genome; and (iii) modeling of abiogenesis.