Fr Francium

Single phases of olivine-type LiCoPO4 and LiNiPO4 were synthesized by thermal treatment of homogeneous lithium-metal-phosphate-formate precursors obtained by freeze drying of aqueous solutions of the corresponding metal formates and LiH2PO4. The structure, thermal behavior, and morphology of the precursors were studied by IR spectroscopy, DTA, and SEM. Cobalt and nickel phosphate-formate precursors have a composition LiMHx(PO4)(HCOO)x·yH2O, where the formate and phosphate groups are mainly deprotonated. For the Co precursor the formate and phosphates ions are randomly coordinated to both Co and Li cations, whereas for the Ni precursor there is a preferential coordination of the formate and phosphate ions around the Ni2+ and Li+ ion, respectively. Thermal treatment of the precursors yields single phases of olivine-type LiCoPO4 at 450 °C and LiNiPO4 at 700 °C. Structural analysis evidences that both LiCoPO4 and LiNiPO4 have an ordered olivine-type structure without any Li to M disorder between the metal positions and lithium deficiency. The effect of the freeze-dried solution concentration and annealing temperature on the structure, crystallite size, and morphology of LiCoPO4 and LiNiPO4 has been discussed. The morphology of the cobalt and nickel phospho-olivines comprises isometric particles with mean sizes of 190 and 380 nm, respectively.

Too groovy: The covalent attachment of up to four porphyrins to complementary strands led to the formation of DNA porphyrin zippers with significantly increased DNA duplex stability. This is a result of H-aggregate formation in the minor groove. To the best of our knowledge this is the first report showing such a significant thermal duplex stabilization.

Bv8, a 77-residue protein isolated from frogs, is the prototypic member of the prokineticin family of cytokines. Prokineticins (PKs) have only recently been identified in vertebrates (including humans), and they are believed to be involved in a number of key physiological processes, such as angiogenesis, neurogenesis, nociception, and tissue development. We used a combination of Boc solid-phase peptide synthesis, native chemical ligation, and in vitro protein folding to establish robust chemical access to this molecule. Synthetic Bv8 was obtained in good yield and exhibited full activity in a human neuroblastoma cell line and rat dorsal root ganglion (DRG) neurons. The 3D structure of the synthetic protein was determined by using NMR spectroscopy and it was found to be homologous with that of mamba intestinal toxin 1, which is the only other known prokineticin structure. Analysis of a truncated mutant lacking five residues at the N terminus that are critical for receptor binding and activation showed no perturbation to the core protein structure. Together with the functional data, this suggests that receptor binding is likely to be a highly cooperative process possibly involving major allosterically driven structural rearrangements. The facile and efficient synthesis presented here will enable preparation of unique chemical analogues of prokineticins, which should be powerful tools for modulating the structure and function of prokineticins and their receptors, and studying the many physiological processes that have been linked to them.

In Alzheimer's disease (AD) and other neurodegenerative disorders, proteins accumulate into ordered aggregates, called amyloids. Recent evidence suggests that these structures include both large, insoluble fibrils and smaller, prefibrillar structures, such as dimers, oligomers, and protofibrils. Recently, focus has shifted to the prefibrillar aggregates because they are highly neurotoxic and their levels appear to correlate with cognitive impairment. Thus, there is interest in finding methods for specifically quantifying these structures. One of the classic ways of detecting amyloid formation is through the fluorescence of the benzothiazole dye, thioflavin T (ThT). This reagent has been a "workhorse" of the amyloid field because it is robust and inexpensive. However, one of its limitations is that it does not distinguish between prefibrillar and fibrillar aggregates. We screened a library of 37 indoles for those that selectively change fluorescence in the presence of prefibrillar amyloid-[beta] (A[beta]). From this process, we selected the most promising example, tryptophanol (TROL), to use in a quantitative "thioflavin-like" assay. Using this probe in combination with electron microscopy, we found that prefibrils are largely depleted during A[beta] aggregation in vitro but that they remain present after the apparent saturation of the ThT signal. These results suggest that a combination of TROL and ThT provides greater insight into the process of amyloid formation by A[beta]. In addition, we found that TROL also recognizes other amyloid-prone proteins, including ataxin-3, amylin, and CsgA. Thus, this assay might be an inexpensive spectroscopic method for quantifying amyloid prefibrils in vitro.

As a starting point, the mononuclear cyclopentadienylmanganese carbonyl thiocarbonyls [CpMn(CS)(CO)n] (Cp = [eta]5-C5H5; n = 2, 1, 0) and binuclear derivatives [Cp2Mn2(CS)2(CO)n] (n = 3, 2, 1, 0) have been studied by density functional theory (DFT). For coordinately saturated binuclear [Cp2Mn2(CS)2(CO)3], the four electron donor end-on CE(E = O, S) bridged structures are preferred energetically over the normal CE (E = O, S) bridged structures, analogous to [Cr2(CS)2(CO)9]. The lowest energy structure for [Cp2Mn2(CS)2(CO)2] has one four-electron donor bridging [eta]2-[mu]-CS group. However, this structure is thermodynamically unstable with respect to disproportionation into [Cp2Mn2(CS)2(CO)3] and [Cp2Mn2(CS)2(CO)]. Only two structures are found for [Cp2Mn2(CS)2(CO)] as is the case for the carbonyl analogue [Cp2Mn2(CO)3]. The global minimum of [Cp2Mn2(CS)2(CO)], a singlet triply bridged structure, is very favorable energetically with respect to loss of a CO group, disproportionation into [Cp2Mn2(CS)2(CO)2] + [(Cp)2Mn2(CS)2], and dissociation into mononuclear fragments. The lowest energy structure for [Cp2Mn2(CS)2] is a triplet structure with two bridging CS groups and the Mn[equiv]Mn triple bond required to give each Mn atom a 17-electron configuration for a binuclear triplet. A higher energy singlet [Cp2Mn2(CS)2] structure is found with a very short Mn[quadruple bond]Mn distance of about 2.1 Å suggesting the formal quadruple bond required to give each Mn atom the favored 18-electron configuration. In other higher energy singlet and triplet [Cp2Mn2(CS)2] structures the two CS ligands have coupled to form an acetylenedithiolate ligand bridging the two manganese atoms.

Neutral tricarbollide tautomers of general formula 7-tBuNH-8,9-R,R[prime]-nido-7,8,9-C3B8H9 (N1), where R,R[prime] = substituents on cage carbon atoms = H, Me, and Ph or their combinations, generated a series of very stable, twelve-vertex ferratricarbollides of general structure [1-Cp-12-tBuNH-2,4-R,R[prime]-closo-1,2,4,12-FeC3B8H8] (2, Cp = [eta]5-C5H5; yields 30-35 %) together with the isomeric complexes [1-Cp-10-tBuNH-2,4-R,R[prime]-closo-1,2,4,10-FeC3B8H8] (3; yields 22-26 %) upon heating with [CpFe(CO)2]2 in mesitylene at reflux for 6 h. Individual compounds were isolated and purified by preparative TLC and characterized by conventional 11B and 1H NMR spectroscopy combined with two-dimensional [11B-11B]-COSY and 1H-{11B(selective)} NMR spectroscopic techniques). The structures of [1-Cp-12-tBuNH-2,4-Me2-1,2,4,12-FeC3B8H8] (2c) and [1-Cp-12-tBuNH-2-Ph-1,2,4,12-FeC3B8H9] (2d) were established by single-crystal X-ray diffraction analysis. Electrochemical studies revealed that the FeII/FeIII redox potentials are primarily affected by the type of the ferratricarbaborane cage and, to a lesser extent, by the Me and Ph substituents residing on the cage carbon atoms.

It's a kind of magic: By using high-resolution magic-angle spinning NMR spectroscopy in combination with hydrogen/deuterium exchange measurements we have shown that at least 18 residues at the N and C termini of [beta]-2-microglobulin aggregated into amyloid fibrils retain a large degree of mobility occurring on different timescales. This study provides insight into the structural architecture of amyloid fibrils of human [beta]-2-microglobulin.

Multivalency is an important phenomenon in protein-carbohydrate interactions. In order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate binding proteins, we displayed them on a microarray surface. Valencies were varied from 1 to 8, and corrections were made for the valencies so that all surfaces contained the same amount of the sugar ligand. Five different carbohydrates were attached to the dendrimers. A series of fluorescent lectins was evaluated, and for each of them a binding profile was obtained from a single experiment showing both the specificity of the lectin for a certain sugar and whether it prefers multivalent ligands or not. Very distinct binding patterns were seen for the various lectins. The results were rationalized with respect to the interbinding distances of the lectins.

A combination of atomic force microscopy, quartz crystal microbalance and fluorescence spectroscopy shed light on the mechanism of interaction of hIAPP with zwitterionic model membranes, and allowed us to speculate the toxic behaviour of hIAPP in diabetes mellitus type II. The results suggest that damage of zwitterionic lipid bilayers and fibrillogenesis are two different phenomena.

Nonpathogenic Mycobacterium species produce rare cyclic C35 terpenes that are biosynthesized by cyclization of Z-type C35 polyprenyl diphosphate. To provide deeper insight into the biosynthesis of C35 terpenes, we carried out functional analyses of three Z-prenyltransferase homologues in M. vanbaalenii identified by genomic analysis. Mvan_3822, a novel bifunctional Z-prenyltransferase, biosynthesizes C35-heptaprenyl diphosphate as a main product from (E,E)-farnesyl diphosphate (E,E-FPP) and (E,E,E)-geranylgeranyl diphosphate (E,E,E-GGPP), but produces a C50-decaprenyl diphosphate from geranyl diphosphate. Mvan_1705 is a novel Z,E,E-GGPP synthase. In addition, novel cyclic C35 terpenes, (14E)- and (14Z)-dehydroheptaprenylcycline, were identified as minor metabolites in nonpathogenic Mycobacterium cells. C35 terpenes could be biosynthesized by two routes, in which E and Z geometric isomers of heptaprenyl diphosphate are produced from E,E-FPP and E,E,E-GGPP, and the prenylreductase responsible for the biosynthesis of C35 terpenes could reduce both E and Z prenyl residues.