A team led by Miquel Coll, researcher with the Consell Superior d'Investigacions Científiques (CSIC), has discovered a DNA structure that could become a new therapeutic target in the treatment of tumours and other pathologies such as Huntington's disease and myotonic distrophy. The study describes a new form of interaction between drugs and DNA, which, according to the authors, would allow the development of a fourth generation of anti-DNA drugs. This research is presented on the cover of Wednesday's issue of the journal Angewandte Chemie.

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Coordinated by Miguel Coll, the team works at the Institut de Biologia Molecular de Barcelona (CSIC) and at the Institute for Research in Biomedicine at the Parc Científic de Barcelona. The research has also involved a team led by Mike Hannon at the University of Birmingham (UK).

First, the Birmingham team developed a synthetic drug with a prismatic triangular structure that, according to Miquel Coll, “resembles the bar of chocolate produced by a famous Swiss firm”. Then, the Barcelona team was able to observe how this drug binds to the DNA and locates in the centre of three-way junction.

These junctions form when three double DNA helices join at one point, and they are observed in diseases such as myotonic dystrophy and Huntington’s disease, the genome of some viruses and in DNA replication, as occurs, for example, in tumour growth.

The new three-way DNA junction discovered leaves a cavity in the centre. The CSIC researcher explains that this cavity is a “perfect” drug target. “Right in the centre, like a police officer in a street crossing before traffic lights were introduced… The drug fits perfectly into this space and blocks DNA”, explained Miquel Coll.

In 1999, this team discovered the junction of four DNA branches or strands, a structure that occurs in the so-called genetic recombination and which is crucial to produce variation or diversity in human beings and other living organisms. However, in contrast to the new structure, the DNA junction previously reported is highly compact, with no cavities or holes in which to couple a drug.

DNA holds the genetic information of human beings and its double helix structure was discovered 50 years ago. Shortly after, research began into DNA-targeting drugs, with the objective to be used to treat cancer and infectious diseases. In the 1960s, three distinct types of anti-DNA drugs were discovered, each of which bound to DNA in a distinct manner. Some of these drugs are currently used in cancer therapies. This new study describes a fourth mechanism through which to attack DNA and opens up a new avenue for drug design.