3- Instead of 4-helix formation in a de novo designed protein in solution revealed by small-angle X-ray scattering

De novo design and chemical synthesis of proteins and their mimics are central approaches for understanding protein folding and accessing proteins with novel functions. We have previously described carbohydrates as templates for the assembly of artificial proteins, so-called carboproteins. Here, we describe the preparation and structural studies of three alpha-helical bundle carboproteins, which were assembled from three different carbohydrate templates and one amphiphilic hexadecapeptide sequence. This heptad repeat peptide sequence has been reported to lead to 4-alpha-helix formation. The low resolution solution structures of the three carboproteins were analyzed by means of small-angle X-ray scattering (SAXS) and synchrotron radiation circular dichroism (SRCD). The ab initio SAXS data analysis revealed that all three carboproteins adopted an unexpected 3+1-helix folding topology in solution, while the free peptide formed a 3-helix bundle. This finding is consistent with the calculated alpha-helicities based on the SRCD data, which are 72 and 68 % for two of the carboproteins. The choice of template did not affect the overall folding topology (that is for the 3+1 helix bundle) the template did have a noticeable impact on the solution structure. This was particularly evident when comparing 4-helix carboprotein monomers with the 2x2-helix carboprotein dimer as the latter adopted a more compact conformation. Furthermore, the clear conformational differences observed between the two 4-helix (3+1) carboproteins based on D-altropyranoside and D-galactopyranoside support the notion that folding is affected by the template, and subtle variations in template distance-geometry design may be exploited to control the solution fold. In addition, the SRCD data show that template assembly significantly increases thermostability.     

Impact of rotifer grazing on population dynamics of green microalgae in high-rate ponds

In high-rate algal ponds, the grazing activity of rotifers such as Brachionus rubens or B. calyciflorus often leads to a replacement of Scenedesmus species by Micractinium pusillum. In contrast to many other green microalgae including Scenedesmus, Micractinium pusillum with fully developed spines (setae) cannot be eaten by Brachionus. Ecological conditions for population shifts between Scenedesmus and Micractinium are, therefore, interpreted as a response of the rotifers rather than being due to physiological properties of the algae. Another effect of rotifer grazing on the microbial flora of high-rate ponds is the development of large stable flocs consisting of bacteria and microalgae.     

Votum der Ethikkommission der Medizinischen Universität zu Lübeck zur Präimplantationsdiagnostik

Ethik in der Medizin -     

Pyryliumverbindungen. XVIII, 2-Alkoxy-2H-pyrane aus tetra- und pentasubstituierten Pyryliumsalzen

Pyrylium Compounds. XVIII. 2-Alkoxy-2H-pyrans from Tetra- and Pentasubstituted Pyrylium Salts Alkali alkoxides add regioselectively to 2,3,4,6-tetrasubstituted pyrylium salts 7 (R' H), affording high yields of colourless crystalline 2-alkoxy-2H-pyrans 9 . The latte are also formed simply on refluxing 7 in the corresponding alcohol with triethylamine as proton acceptor. 3,5-Dialkylsubstituted 2,4,6-triarylpyrylium salts react analogously. The 2H-pyran structure of the adducts obtained follows from their n.m.r., i.r., u.v. and mass spectra as well as from their reaction with tetracyanoethylene to cycloadducts of type 10 . Acids regenerate from 9 the original pyrylium cations, whereas reaction of 9 with nitromethane or ethyl cyanoacetate provides benzene derivatives. -- The novel starting pyrylium salts 7b--o are characterized by u.v./vis data and by transformation into the corresponding pyridine derivatives     

Radikalabfang. III [1] ESR-spektroskopische Untersuchung von Radikalreaktionen eines bicyclischen 1-Hydroxy-3-imidazolin-3-oxids [2]

Spin Trapping. III. Studies of Radical Reactions of a Bicyclic 1-Hydroxy-3-imidazoline-3-oxide Radical addition reactions to the nitrono group and the oxidation of the 8-hydroxy-1,4,5,7-tetramethyl-6,8-diazabicyclo[3.2.1]oct-6-en-6-oxide 2b were investigated by e.s.r.-spectroscopy. Oxidation of 2b by Ag₂O, PbO₂, hydrogenperoxide, tert.-butoxy and benzoyloxy radicals, respectively, yields a bicyclic nitroxide with typical a(N)-value (1,9 mT). Testing a wide range of carbon-centered radicals we did not find, however, any spin adducts in contrast to the literature. Only H-atoms are found to add to the nitrone function of 2b giving a bicyclic nitroxide 4b (R′ = H) with a(N)-value of 1,4 mT, a(H_ax) = 2,4 mT. The relationship between a ring-chain tautomerism of 2 as previously described and the formation of radicals has been demonstrated by radical reactions of derivatives of ring opened isomers 5b .     

The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

Reaktionen des 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyradikals

Reactions of the 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyl Radical The title compound, a phenoxyl radical containing a nitrono group, reacts with alcohols and tert.-butylhydroperoxide yielding phenol and products of secondary radical solvent reactions. The reactions with lead tetraacetate, tert.-butoxy and 2-cyanoisopropyl radicals give high yields of cyclohexadienone adducts ( 6, 7 and 10 ) containing unchanged nitrono function. The reaction with dibenzoylperoxide, however, leads to the modification of the nitrono group yielding the N-benzoyloxycarboxamide ( 8 ). In the acidic decomposition of the tert.-butoxy radical adduct we suggest a nitrenium ion ( 16 ) as an intermediate.