How do you study DNA without affecting it? Chemists have linked fluorescent tags to DNA to minimise unwanted interactions with the double helix.

Cyanine dyes are among the oldest classes of synthetic compounds and are used as fluorescent labels for DNA, proteins and other biomolecules. Shankar Balasubramanian and colleagues at the University of Cambridge, UK, attached these dyes to DNA by a rigid ethynyl linker.

Conventional, widely-used methods to attach cyanine dyes to DNA employ a flexible linker instead, explains Balasubramanian. 'We and others have shown that this results in a dye-DNA interaction that alters the stability of the DNA double helix.' In contrast, the UK team found that using the rigid ethynyl linker fixed the dye's geometry and position, preventing it from interacting with the DNA helix and so changing its stability and structure.

'It is an enduring challenge to develop tags that accurately report on - without perturbing - biomolecule structure and/or function,' says Bruce Armitage from Carnegie Mellon University, in Pittsburgh, US, who works in the field of biomolecule recognition. 'This rigid linker elegantly achieves this elusive goal.'

'There is considerable interest in labelling DNA and RNA with fluorescent dyes for a range of applications that include fluorescence biophysics, genetic analysis, gene sequencing and nanoscience,' says Balasubramanian, explaining his motivation for the work.

Duncan Graham, a DNA researcher from the University of Strathclyde, in Glasgow, UK, agrees that the new method has potential for biological science. 'This work has implications in many areas of bioanalysis where optical spectroscopy can be used to rapidly acquire 3D information,' he says. 'The rigid linker fixes the dyes' positions in space, which is important when using a technique which relies on spatial interactions to provide an accurate distance measurement on a nanometre scale,' he explains. 'The system offers improvements in terms of potential resolution and the ability to examine dynamic systems in real time.'

Sarah Corcoran