New DNA recognition method determines drug design
themselves to DNA, providing a crucial step forward for those who
are developing drugs to combat cancer and other diseases. The
breakthrough heralds a new way of recognising DNA, which will
hopefully lead to a new approach in designing drugs.
Scientists soon started designing drugs to target DNA and used them to treat diseases such as cancer, viral infections and sleeping sickness.
In the 1960s, scientists discovered three different classes of clinical drug, each of which recognised DNA in a different way. Subsequent drugs have used only these three ways to recognise the DNA.
Now this latest research has isolated a fourth, which is completely different and opens up entirely new possibilities for drug design.
The scientists, from Barcelona and Birmingham, have developed a synthetic drug agent that targets and binds to the centre of a 3-way junction in the DNA. These 3-way junction structures are formed where three double-helical regions join together.
They are particularly exciting as they have been found to be present in diseases, such as some Huntington's disease and myotonic dystrophy, in viruses and whenever DNA replicates itself, for example, during cancer growth.
The Birmingham team created a nanosize synthetic drug in the shape of a twisted cylinder. Together with researchers in the UK, Spain and Norway they showed that is had unprecedented effects on DNA.
Now molecular level pictures taken by the Barcelona team have shown that it binds itself in a new way to the DNA, by fixing itself to the centre of a DNA junction, which had three strands.
It is all held together because the cylinder is positively charged and the DNA is negatively charged. In addition the drug is a perfect fit in the heart of the junction: a round peg in a round hole.
"This is a significant step in drug design for DNA recognition and it is an absolutely crucial step forward for medical science researchers worldwide who are working on new drug targets for cancer and other diseases," said Mike Hannon, from the University of Birmingham's School of Chemistry.
"This discovery will revolutionise the way that we think about how to design molecules to interact with DNA. It will send chemical drug research off on a new tangent. By targeting specific structures in the DNA scientists may finally start to achieve control over the way our genetic information is processed and apply that to fight disease."
A number of current anti-cancer drugs target disease at DNA level, but they are not specific in their approach and this means that they can cause unpleasant side effects.
Moreover some of these drugs suffer from developed resistance as the body learns how to deal with drugs that act in a particular way. By creating drugs, which act in completely different ways, this acquired resistance could be overcome.
