New molecular tools for the 21st century: Molecular design of new DNA-based devices

The overall objective of this work is to develop methods for the organisation of metals and magnets along a DNA template. In this research we will develop a new chemical biological approach for the construction of electronic and information storage devices based on the genetic code of DNA. We will use organic chemistry to make molecules that will effectively "read" the genetic code of DNA. We will then investigate whether we can use this code as an address book in order to send a particular metal or a magnet to a particular destination along the DNA template. We will also use biology to manipulate and fine tune DNA structures using various enzymes. This will allow us to create ordered structures of complexity not achieved in today's circuits.

The aims of this project in order of priority are:

1. To develop a fundamental suite of methods that enables the selective deposition of conductive, semi-conductive and magnetic materials along a DNA template using enzymatic and molecular recognition methods.

2. To determine the conductive, semi-conductive and magnetic properties of the resulting nucleic acid programmed materials.

3. To utilise this technology for the fabrication of cost-effective and efficient molecular electronic, information storage and diagnostic devices.

This fellowship has progressed the current state of the art of DNA nanotechnology in areas relating to supramolecular chemistry, organic synthesis and photonics.

The specific discoveries arising from this fellowship are:
1. DNA-programmed photonic assemblies
GAB’s group has recently developed a new design paradigm for directing light energy along DNA duplexes (dsDNA) and DNA nanostructures. DNA-binding polyamides were shown to direct the insertion of an intercalating oxazole yellow (YO) dye within dsDNA at pre-determined binding sites to produce the longest reported DNA photonic wire. This work highlights GAB’s ability to prepare challenging DNA binding agents and paves the way for the downstream exploitation of these concepts to “clip on” functionality in more sophisticated NA nanostructures.
Outputs:
[GAB1] Su, W., Bagshaw, C.R., Burley, G.A. "Addressable and unidirectional energy transfer along a DNA three-way junction programmed by pyrrole-imidazole polyamides" Scientific Reports, 2013, 3, 1883.
[GAB2] Su, W., Bonnard, V.B., Burley, G.A. "DNA-templated photonic arrays and assemblies: Design principles and future opportunities" Chemistry - A European Journal, 2011, 17, 7982-7991.
[GAB3] Su, W., Schuster, M., Bagshaw, C.R., Rant, U., Burley, G.A. "Site-specific assembly of DNA-based photonic wires by using programmable polyamides" Angewandte Chemie International Edition, 2011, 50, 2712-2715.

2. New methodologies to prepare DNA diagnostic devices.
Using GAB’s patented method of PA synthesis, PAs were highly effective at directing gold nanoparticle aggregation in the presence of dsDNA sequences incorporating target PA binding sites. In addition, PAs were also highly versatile compounds to detect fluorescently-tagged dsDNA sequences with high selectivity when immobilised on solid substrates. This work gives confidence that minor groove binding ligands can direct the assembly of large molecular weight materials in a sequence selective manner along dsDNA motifs.
Outputs:
[GAB4] Singh, I., Wendeln, C., Clarke, A.W., Cooper, J.M., Ravoo B.J., Burley, G.A. "Sequence-selective detection of double-stranded DNA sequences using pyrrole-imidazole polyamide microarrays" Journal of the American Chemical Society, 2013, 135, 3449-3457.
[GAB5] Binns, C.; Prieto, P.; Baker, S.; Howes, P.; Dondi, R.; Burley, G.; Lari, L.; Kroeger, R.; Pratt, A.; Aktas, S.; Mellon, J.K. "Preparation of hydrosol suspensions of elemental and core–shell nanoparticles by co-deposition with water vapour from the gas-phase in ultra-high vacuum conditions" Journal of Nanoparticle Research, 2012, 14, 1136.
[GAB6] Haughey, A-M., Guilhabert, B., Kanibolotsky, A.L., Skabara, P.J., Dawson, M.D., Burley, G.A., Laurand, N. "An oligofluorene truxene based distributed feedback laser for biosensing applications" Biosensors and Bioelectronics,2013, in press.
[GAB7] Haughey, A-M., Guilhabert, B., Skabara, P.J., Burley, G.A., Dawson, M.D., Laurand, N. "An organic semiconductor laser based on star-shaped truxene-core oligomers for refractive index sensing" Sensors and Actuators B: Chemical, 2013, 185,132-139.
[GAB8] Wendeln, C., Singh, I, Rinnen, S., Schulz, C., Arlinghaus, H.F., Burley, G.A., Ravoo B.J. "Orthogonal, metal-free surface modification by strain-promoted azide-alkyne and nitrile oxide-alkene/alkyne cycloadditions" Chemical Science, 2012, 3, 2479-2484.
[GAB9] Krpetic, Z., Singh, I., Su, W., Guerrini, L., Faulds, K., Burley, G.A., Graham, D. "Directed Assembly of DNA-Functionalized Gold Nanoparticles Using Pyrrole-Imidazole Polyamides" Journal of the American Chemical Society,2012, 134, 8536-8539.
[GAB10] Zon, V. B., Burley, G.A., Rant, U. "Photo-induced growth of DNA-capped silver nanoparticles" Nanotechnology, 2012,23, 115607.
[GAB11] Berti, L., Burley, G. A., "Nucleic acid and nucleotide-mediated synthesis of inorganic nanoparticles" Nature Nanotechnology, 2008, 3, 81-87.
[GAB12] Su, W..; Burley, G. A.; "New process and new compounds." (2010), WO2010/125382 PCT/GB2010/050687