Novel screening method speeds up cancer drug search
vastly speed up the search for new cancer drugs and antibiotics
that has proved problematic and time expensive in the drug's
development cycle.
The technique has generated excitement within the research community as a quicker and more accurate screen will allow more potential drugs to be assessed and thus aid the search for urgently needed new anti-cancer and antibacterial drugs.
The screening method works by measuring the activity of a group of enzymes called DNA topoisomerases that help package DNA.
The researchers think that chemicals that block these enzymes could be developed into new anti-cancer and anti-bacterial drugs.
Members of the topoisomerase family such as DNA gyrase promote supercoiling of DNA and are targets for antibacterials; another member of the family, human Topo II relaxes DNA supercoils and is an anti-cancer drug target.
DNA normally forms a duplex molecule consisting of two strands, but under certain conditions it can be encouraged to bind a third strand to form a triplex molecule.
Triplex DNA is more readily formed by supercoiled DNA so the activity of the topoisomerase can be determined by measuring the amount of triplex DNA present.
The triplex-forming third DNA strand is tethered to a multi-well plate and captures supercoiled DNA which is then detected using a fluorescent stain.
In this way, chemical libraries can be screened for their ability to inhibit the topoisomerase and assessed for their potential as drugs.
"A patent for the technique has been granted and we already have several pharmaceutical companies that are interested in licensing the technology," said Tony Maxwell, leader of the John Innes Centre (JIC) scientific team.
The previous method used for measuring the activity of topoisomerases is time consuming and labour-intensive.
Maxwell thinks that this new technique is faster, more accurate and could be automated with robotics to screen thousands of chemicals and identify those with the potential to be made into drugs.
This work is available online in advance of printed publication in Nucleic Acids Research (Maxwell et al, >"High-throughput assays for DNA gyrase and other topoisomerases").
