Shedding light on the reaction mechanism of PUVA light therapy for skin diseases

Psoralens insert between the crucial building blocks (bases) of DNA, the hereditary molecule. When subjected to UV radiation, they bind to thymine -- a specific DNA base -- and thus cause irreversible damage to the hereditary molecule. This in turn triggers programmed cell death, ultimately destroying the diseased cell.

Researchers working with Prof. Dr. Peter Gilch from HHU's Institute of Physical Chemistry have now collaborated with Prof. Dr. Wolfgang Zinth's work group from LMU Munich to analyse the precise mechanism of this binding reaction. They used time-resolved laser spectroscopy for this purpose.

They found that -- after the psoralen molecule has absorbed UV light -- the reaction takes place in two stages. First, a single bond between the psoralen molecule and thymine forms. A second bond formation then yields a four-membered ring (cyclobutane) permanently connecting the two moieties. The researchers in Düsseldorf and Munich were also able to demonstrate that the first stage takes place within a microsecond, while the second needs around 50 microseconds. They compared this process with the damaging of the 'naked' DNA by UV light. That process also frequently results in cyclobutane rings, but the process takes place considerably faster than when psoralens are present.

Prof. Gilch explains the background to the research: "If we can understand how the reactions take place in detail, we can change the psoralens chemically in a targeted way to make PUVA therapy even more effective." Together with his colleague in organic chemistry, Prof. Dr. Thomas Müller, he wants to develop these high-performance psoralen molecules at HHU within the scope of a DFG project.