Search

The Natura 2000 network of protected areas is the backbone of species conservation in the European Union. We investigated whether Austrian-hatched white-tailed eagles (Haliaeetus albicilla) make particular use of this multinational network during their natal dispersal, and what habitats were of importance to the eagles. We analyzed the utilization distribution of 907,466 GPS locations from 38 dispersing white-tailed eagles using a dynamic Brownian Bridge Movement Model. Eagles ranged over a huge area of central-eastern Europe. Natura 2000 sites overlapped with 67% of the resulting 50% isopleth; i.e., a high probability of utilization of Natura 2000 areas by white-tailed eagles was found. White-tailed eagles used wetlands, waterbodies, and deciduous forests adjacent to wet habitats disproportionately often. Coniferous forests and settlements were avoided. Anthropogenically caused mortalities hardly occurred within Natura 2000 sites. Our study suggests that the Natura 2000 network is a crucial tool for conserving the white-tailed eagle. This top predator is an ambassador for the Natura 2000 idea during all life stages, and should continue to be a conservation priority of the network.

In this study, we report on the modification of a 3,4-diaryl-isoxazole-based CK1 inhibitor with chiral pyrrolidine scaffolds to develop potent and selective CK1 inhibitors. The pharmacophore of the lead structure was extended towards the ribose pocket of the adenosine triphosphate (ATP) binding site driven by structure-based drug design. For an upscale compatible multigram synthesis of the functionalized pyrrolidine scaffolds, we used a chiral pool synthetic route starting from methionine. Biological evaluation of key compounds in kinase and cellular assays revealed significant effects of the scaffolds towards activity and selectivity, however, the absolute configuration of the chiral moieties only exhibited a limited effect on inhibitory activity. X-ray crystallographic analysis of ligand-CK1δ complexes confirmed the expected binding mode of the 3,4-diaryl-isoxazole inhibitors. Surprisingly, the original compounds underwent spontaneous Pictet-Spengler cyclization with traces of formaldehyde during the co-crystallization process to form highly potent new ligands. Our data suggests chiral “ribose-like” pyrrolidine scaffolds have interesting potential for modifications of pharmacologically active compounds.