New analytical methods for the study of pteridine compounds and the chemistry of their interactions with free radicals

Aim of the of the described project was to investigate the interactions of pteridines with free radicals. A number of different methods for the detection of radicals and their reactions have been used. The work was focussed on dihydropterins, especially dihydroneopterin. It was generally accepted that dihydropterins act as radical scavengers. However, we could show that it depends extremely on the experimental conditions whether dihydroneopterin acts as a scavenger of free radicals or promotes the formation of these species. The presence of metal ions, e.g. iron or copper, is critical. In principle dihydroneopterin is a scavenger of free radicals but in the presence of only trace amounts of iron or copper ions the reducing power of dihydroneopterin leads to the formation of oxygen free radicals. We further investigated the influence of dihydroneopterin on other reactive species like peroxynitrite and free radicals resulting from ist decay. Again we found different effects, depending on the experimental design. Radical scavenging, however, was the predominant effect. Based on these experiments using simple chemical systems, we started investigating the effects of dihydroneopterin on free radical mediated reactions in biochemical and biological systems. We found that the inhibitory effect of dihydroneopterin on oxidation of low density lipoprotein (LDL) stimulated by copper ions turns into a prooxidative effect if not native LDL but minimally oxidized LDL is used. Therefore, dihydroneopterin could help the macrophage to distinguish between native LDL which should be protected, and minimally oxidized LDL which should be further modified to be bound by the scavenger receptor of the macrophage. Apoptosis of T lymphocyte which in general is influenced by the redox environment of a cell, is also influenced by the presence of dihydroneopterin in the cell culture medium.