Chemical ligation

Three-dimensional image of a DNA catenane synthesized using click chemistry Our research has very recently moved in a new direction. We are using the copper-catalysed alkyne-azide coupling reaction (click chemistry) to synthesise large, covalently closed cyclic DNA structures and catenanes for use in biological applications e.g. as decoys for transcription factors, and as scaffolds in nanotechnology.

Our first paper in this field was one of the most cited JACS papers in 2007 (View paper), and two other publications (View paper, View paper) were amongst the most accessed papers when they appeared on the ChemBioChem web site.

Recent collaborations with Prof. Bengt Norden’s group in Gothenburg involved the use of DNA click chemistry to elucidate the binding mechanism of a novel threading DNA intercalator (View paper) and led to the synthesis of addressable high-information-density DNA nanostructures (View paper). These constructs constitute scaffolds on which molecules can be attached at pre-determined locations with nanometre precision so that they can communicate in a controlled manner by energy or electron transfer. This is a new bottom-up approach to nanotechnology and relies heavily on our skills is DNA chemistry.

Most recently we have developed a new version of our oligonucleotide ligation chemistry to synthesise DNA templates containing modified backbones which can be copied by polymerases during PCR. This exciting new discovery (View paper) promises to open up a new field, as it suggests that the synthesis of DNA strands greater than 1000 bases in length by entirely chemical methods is within reach. This is an order of magnitude longer than is achievable by existing methods, and could lead to important developments in biotechnology.