The first entirely new approach to DNA recognition since the year of my birth has been developed by Mike Hannon and colleagues at the University of Birmingham and Miquel Coll at the Spanish Research Council in Barcelona. The team has discovered a new route through which drug molecules can attach themselves to DNA. The researchers say this is a crucial step forward in drug discovery, the first in four decades.
The scientists have developed a synthetic agent that targets and binds to the centre of a three-way junction in DNA. Such junctions are formed where three double-helical regions join together and 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 are present during cancerous cell replication.
The Birmingham team created a nanosize synthetic drug shaped like a twisted cylinder. Together with colleagues in the UK, Spain and Norway they previously demonstrated its unprecedented effect on DNA. Now, structures revealed by the Barcelona team show that it binds to DNA in an entirely novel way – fixing itself to the centre of a 3-way junction. The resulting complex is held electrostatically. The researchers explain that the drug fits like a round peg in a round hole.
According to Hannon, “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. 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.”
Let’s just hope that quote from Birmingham University’s press release on this research bears fruit, I’d hate to think that a discovery that’s waited my whole life to be made will be anything less than a breakthrough of unprecedented scale.
The work appears in the February 8 issue of Angewandte Chemie.