New technique will help search for new cancer drugs and antibiotics30 August 2006 A team of John Innes Centre (JIC) scientists led by Prof Tony Maxwell have developed a new technique that will help search for new anti-cancer and anti-bacterial drugs more quickly and accurately. The researchers found a new way of measuring the activity of a group of enzymes called DNA topoisomerases that help package DNA, the molecule that stores genetic information, into cells. Chemicals that block these enzymes could be developed into new anti-cancer and anti-bacterial drugs. The previous method used for measuring the activity of topoisomerases is time consuming and labour-intensive; 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 development is really exciting because it will speed up the whole discovery process for this type of drug. A quicker and more accurate screen will allow more potential drugs to be assessed and therefore aid the search for urgently needed new anti-cancer and antibacterial drugs” says Tony Maxwell. “A patent for the technique has been granted and we already have several pharmaceutical companies that are interested in licensing the technology”. The technique has been patented and will be marketed by PBL, the technology management company of the John Innes Centre, and will be further developed by Inspiralis Ltd, a spin-out company housed in the Norwich Bioincubator. The research was funded by the BBSRC and PBL and is published online in the peer-reviewed journal Nucleic Acids Research. Notes for editorsFor further information, images or to arrange an interview with Prof Maxwell, please contact Vicky Just at the Norwich Bioscience Institutes Press Office on +44 (0)1603 255111, email Victoria.just@jic.ac.uk . How the screen works DNA is a very long molecule and requires topoisomerases to wind it tightly or “supercoil” it to fit into the cell. 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. 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"). http://nar.oxfordjournals.org/ The John Innes Centre Inspiralis Ltd Plant Bioscience Limited (PBL) |