Background: Night-migratory birds sense the Earth’s magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that the light-induced formation of a radical-pair in European robin cryptochrome 4a (ErCry4a) is the primary signaling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signaling involving the α-subunit of the cone-secific heterotrimeric G protein from European robin. Methods: Protein–protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer. Results: Surface plasmon resonance studies showed direct interaction, revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer. Conclusions: Our results suggest that ErCry4a and the G protein also interact in living cells and might constitute the first biochemical signaling step in radical-pair-based magnetoreception.

Background: Night-migratory birds sense the Earth´s magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that light-induced formation of a radical-pair in European robin cryptochrome 4a, ErCry4a, is the primary signalling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signalling involving the α-subunit of the cone specific heterotrimeric G protein from European robin. Methods: Protein-protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer. Results: Surface plasmon resonance studies showed direct interaction revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer. Conclusions: Our results suggest that ErCry4a and the G protein also interact in vivo and might constitute the first biochemical signalling step in radical-pair-based magnetoreception.

Two series of nucleolipids, O-2',3'-heptanylidene- as well as O-2',3'-undecanylidene ketals of six β-d-ribonucleosides (type A) and partly N-farnesyl derivatives thereof (type B) were prepared in a combinatorial manner. All novel compounds were characterized by elemental analysis and/or ESI mass spectrometry and by UV-, H-, and C-NMR spectroscopy. Conformational parameters of the nucleosides and nucleolipids were calculated from various J(H,H), J( H, C), and J(F,H) coupling constants. For a drug profiling, the parent nucleosides and their lipophilic derivatives were studied with respect to their distribution (log P) between water and n-octanol as well as water and cyclohexane. From these data, qualitative conclusions were drawn concerning their possible blood-brain barrier passage efficiency. Moreover, nucleolipids were characterized by their molecular descriptor amphiphilic ratio (a.r.), which describes the balance between the hydrophilicity of the nucleoside headgroup and the lipophilicity of the lipid tail. All compounds were investigated in vitro with respect to their cytostatic/cytotoxic activity toward human glioblastoma (GOS 3) as well as rat malignant neuroectodermal BT4Ca cell lines in vitro. In order to differentiate between anticancer and side-effects of the novel nucleolipids, they were also studied on their activity on differentiated human THP-1 macrophages.

A class of light-activated proteins in the eyes of birds, called cryptochromes, are thought to act as the primary magnetic sensors allowing night-migratory songbirds to navigate over thousands of kilometers using the earth’s magnetic field. Having evolved from DNA-repairing photolyases, cryptochromes have redirected the energy from light to fuel a variety of other functions: as photoreceptors, as regulators of the circadian clock – and, in some species, most likely as sensors of the magnetic field. While the quantum effects of magnetic fields on cryptochromes are already being studied in detail, almost nothing is known about the signaling cascade involving cryptochrome as the primary receptor protein. Two different screening methods have identified potential interaction partners that suggest an involvement of the visual phototransduction pathway, the visual cycle, potassium channels or glutamate receptors, but more pioneering research is needed to unravel the signaling cascade responsible for transducing the magnetic signal.

The stabilizing neighboring effect of halo substituents on silyl cations was tested for a series of peri‐halo substituted acenaphthyl‐based silyl cations 3. The chloro‐ (3 b), bromo‐ (3 c), and iodo‐ (3 d) stabilized cations were synthesized by the Corey protocol. Structural and NMR spectroscopic investigations for cations 3 b–d supported by the results of density functional calculations, which indicate their halonium ion nature. According to the fluorobenzonitrile (FBN) method, the silyl Lewis acidity decreases along the series of halonium ions 3, the fluoronium ion 3 a being a very strong and the iodonium ion 3 d a moderate Lewis acid. Halonium ions 3 b and 3 c react with starting silanes in a substituent redistribution reaction and form siliconium ions 4 b and 4 c. The structure of siliconium borate 4 c2[B12Br12] reveals the trigonal bipyramidal coordination environment of the silicon atom with the two bromo substituents in the apical positions.