title: Thermal stability of DNA quadruplex-duplex hybrids.
abstract: DNA has the capacity to adopt several distinct structural forms, such as duplex and quadruplex helices, which have been implicated in cellular processes and shown to exhibit important functional properties. Quadruplex-duplex hybrids, generated from the juxtaposition of these two structural elements, could find applications in therapeutics and nanotechnology. Here we used NMR and CD spectroscopy to investigate the thermal stability of two classes of quadruplex-duplex hybrids comprising fundamentally distinct modes of duplex and quadruplex connectivity: Construct I involves the coaxial orientation of the duplex and quadruplex helices with continual base stacking across the two components; Construct II involves the orthogonal orientation of the duplex and quadruplex helices with no base stacking between the two components. We have found that for both constructs, the stability of the quadruplex generally increases with the length of the stem-loop incorporated, with respect to quadruplexes comprising nonstructured loops of the same length, which showed a continuous drop in stability with increasing loop length. The stability of these complexes, particularly Construct I, can be substantially influenced by the base-pair steps proximal to the quadruplex-duplex junction. Bulges at the junction are largely detrimental to the adoption of the desired G-quadruplex topology for Construct I but not for Construct II. These findings should facilitate future design and prediction of quadruplex-duplex hybrids.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore 637371.
authors.forename: Kah Wai
authors.initials: KW
authors.lastname: Lim
authors.forename: Zi Jian
authors.initials: ZJ
authors.lastname: Khong
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D020029:Base Pairing; D001669:Biochemical Phenomena; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA