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This thesis is concerned with the rational design of a group of DNA higher order architectures known as quadruplex DNA. Quadruplex DNA is comprised of a stem of stacking guanine tetrads linked by loops comprised of single stranded DNA. Due to the different combinations of loop types possible, it has great structural diversity and has potential nanotechnological and biological applications. Currently, only a few loop combinations, or topologies are known. Those that have been determined experimentally were not explicitly designed. Using a geometric formalism, the sum of currently available knowledge on quadruplex folding was used to create a set of parameters for the design of novel quadruplex architectures. We present the proof of principle for rational design of said structures, through making the novel topology (-pd+l) and the (G:C:G:C) tetrad- containing topology -(Ppp). We apply this principle to interpret thermal difference spectra signatures of a number of designed quadruplexes. Finally, we show that such novel quadruplexes can be used as building blocks for nanowires. This thesis therefore describes the proof of principle of design, means to expediate design, and an example application of design, of quadruplex nucleic acids. Through achieving these three aims, we present the feasibility of designing novel quadruplexes to be used as nanotechnological or medical devices. |
