Photo-dynamic therapy, a form of treatment for a number of conditions including several cancers and psoriasis, is an area of intense research activity. This treatment strategy uses light to activate a drug in a specific area of the body and can reduce the side effects observed through conventional anti-cancer treatments.
Now a group of scientists working in Reading and Dublin have published a new way of finding out how such compounds work at a fundamental level, the information from which can be used to improve anti-cancer drug development.
It is really difficult to observe such fast processes in living cells, but the much simpler environment of a DNA crystal has enabled the team to watch the initial crucial step in great detail. The new method is published today (19 October) in the leading chemical journal Nature Chemistry.
The crystals contain a ruthenium compound which is bound to a short piece of DNA. This class of compound is used in DNA sensing and is of interest to the pharmaceutical industry for cancer treatment.
The researchers found that by using infrared radiation, they could get a snapshot of the extremely fast process – which occurs in half a billionth of a second – that takes place when light is shone on the crystals. This activates the compound, making it cause damage to DNA.
This research was carried out using two UK central research facilities: the laser facilities in the Central Laser laboratory of the Science and Technology Facilities Council (STFC) and Diamond Light Source, the UK national synchrotron facility.
Dr Susan Quinn, from the School of Chemistry at University College Dublin is the lead author of the study. She said: “These results are very exciting as they demonstrate the ability to follow the flow of electrons from DNA to a molecule whose exact position is known and this is an enormous advantage in the study of the early events that lead to DNA damage.”
Professor Christine Cardin, from the University of Reading, is a nucleic acid crystallographer who led the UK team, including co-author Dr James Hall, and who has received major funding from BBSRC in support of this work. She said: “This work is an exciting step in helping us to understand DNA damage. Among other things, the insights from this study will feed into the development of new drugs that target cancerous tissue, without damaging healthy tissue around it.
“This paper is one result of a longstanding collaboration with Professor John Kelly in Trinity College Dublin, and an excellent example of multidisciplinary international collaboration.
“It also highlights the benefits of combining the facilities of Diamond Light Source, where all the crystallography has been carried out, with the equipment and expertise available in the adjacent Central Laser Facility of the STFC.”
A key element of the funding for the collaboration has been provided by the Royal Irish Academy-Royal Society exchange programme, running since 2008 between Trinity College Dublin and the University of Reading.
Read Nature Chemistry at www.nature.com/nchem/index.html
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