We are interested in the synthesis of chemically-modified nucleic acids, for use in structural characterisation of DNA, RNA, and associated protein complexes. Our primary interest lies in the application of EPR spectroscopy to biomolecule distance measurements, where we collaborate with Dr Janet Lovett (St. Andrews) and Prof Tom Brown (Oxford).
We have developed a base-independent method for spin labelling of oligonucleotides, which is centred on the use of 2'-alkynyl nucleosides. These are constructed by an atom transfer radical addition (ATRA) reaction to migrate an alkyne residue from the 3' oxygen atom of the ribose framework, to the 2' carbon atom. This approach allows great diversity in the types of spin labels we attach to the duplex, using copper-catalyzed azide-alkyne cycloaddition.
Our ongoing work extends to other modes of characterization, such as X-ray crystallography (with Dr Denis Ptchelkine, Oxford), Molecular dynamics (with Dr Frank Beierlein, Friedrich-Alexander-Universität, Erlangen-Nürnberg), and NMR (Prof Andrew Lane, Nebraska), and to applications of the technology to study dynamic biological processes.