Role of loops in the guanine quadruplex formation by DNA/RNA hybrid analogs of G sub(4)T sub(4)G sub(4)

CD spectroscopy, gel electrophoresis and absorption-based thermal stability were used to analyze quadruplex formation of RNA and RNA/DNA hybrid analogs of the deoxyoligonucleotide G sub(4)T sub(4)G sub(4), which forms a well- characterized basket-type quadruplex. All RNA-containing dodecamers, g sub(4)u sub(4)g sub(4), G sub(4)u sub(4)G sub(4) and g sub(4)T sub(4)g sub(4) (RNA lower- case, DNA capital letters), formed parallel, namely tetramolecular quadruplexes in Na super(+)-containing solutions. The u sub(4) loop forced DNA tetrads into the same conformation as adopted by g sub(4)u sub(4)g sub(4). In contrast, the T sub(4) loop destabilized the RNA tetrads. Potassium ions markedly stabilized parallel quadruplexes of RNA-containing analogs as well as their bimolecular folding. In the presence of K super(+), g sub(4)T sub(4)g sub(4) formed exclusively bimolecular quadruplexes of both parallel and antiparallel types as indicated by CD. Thus, the T sub(4) loop permits RNA strands to adopt an antiparallel arrangement. These findings may be useful for engineering particular quadruplex foldings in different quadruplex-forming sequences.