Role of loops in the guanine quadruplex formation by DNA/RNA hybrid analogs of G4T4G4

CID 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(4)T(4)G(4), which forms a well-characterized basket-type quadruplex. All RNA-containing dodecamers, g(4)u(4)g(4), G(4)U(4)G(4) and g(4)T(4)g(4) (RNA lower-case, DNA capital letters), formed parallel, namely tetramolecular quadruplexes in Na+-containing solutions. The u(4) loop forced DNA tetrads into the same conformation as adopted by g(4)u(4)g(4). In contrast, the T-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+, g(4)T(4)g(4) formed exclusively bimolecular quadruplexes of both parallel and antiparallel types as indicated by CD. Thus, the T-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. (C) 2008 Elsevier B.V. All rights reserved.