Photochromic control of nucleic acid systems through anthracene photodimerisation

Manchester, Jack Nathaniel (2014). Photochromic control of nucleic acid systems through anthracene photodimerisation. University of Birmingham. Ph.D.

Preview

Manchester14PhD.pdf
PDF - Accepted Version
Download (13MB)

Abstract

The focus of this project has involved the incorporation of non-nucleosidic anthracene phosphoramidites into oligonucleotide sequences for the purpose of studying anthracene photodimerisation and its effect on DNA structure and function. The primary aim of the research was to use this technique as a method of disrupting hybridisation between complementary oligonucleotides.
By introducing two anthracene tags into the same oligonucleotide sequence it is possible to initiate a reversible, light-induced reaction involving the intramolecular dimerisation of the appended anthracene groups. The resulting change in structure, combined with a change in π-stacking interactions within the oligonucleotide, alters the binding towards the complementary sequence. This effect was studied through a number of techniques including variable temperature UV, CD and fluorescence spectroscopy and gel electrophoresis.
A range of studies have been employed that utilise this technique, principally investigating whether the release of a bound complementary oligonucleotide can be achieved by completely destabilising the intermolecular interactions. However the study has been expanded to investigate known G-quadruplex sequences and how their interactions with proteins can be altered. Finally the intermolecular photodimerisation between two anthracene modified oligonucleotides was investigated in order to create temporary cross links, which can help stabilise the duplex structure.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):