Strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation

A strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation using poly(lysine) dendritic wedges as scaffolds is presented.     

Isomorphous substitution in bimetallic oxide clusters

The geometric and electronic structure of bimetallic oxide clusters is studied as a function of their composition with gas phase vibrational spectroscopy. Infrared multiple photon dissociation spectra of titanium-vanadium oxide cluster anions are measured in the 500 to 1200 wave number range and assigned on the basis of harmonic frequencies calculated using density functional theory. Singly substituted (V(2)O(5))(n-1)(VTiO(5))(-) (n=2-4) cluster anions are shown to form polyhedral caged structures similar to those predicted for their isoelectronic counterparts, the neutral (V(2)O(5))(n) clusters. Upon systematic exchange of V by Ti atoms in V(4-n)Ti(n)O(-)(10) (n=1-4), the structure does not change. The stress induced by the isomorphous substitution results in an increased number of unpaired electrons (n-1) for the Ti-rich systems, leading to a quartet ground state for Ti(4)O(-)(10).     

Mineral zircon: A novel thermoluminescence geochronometer

Mineral zircon contains trace amounts (typically 10-1000 v ppm) of the f -emitters uranium and thorium, which irradiate this mineral internally. This outstanding feature of zircon turns out to be extremely useful when this mineral is applied as a thermoluminescence (TL) dating medium, because the build-up of the age-dependent luminescence is dominated by the presence of well-defined internal radioactive sources and the contributions to the dose from external radiation sources are two orders of magnitude smaller. The results presented in this paper have led us to the conclusion that for zircon dating it is necessary to carefully select the best and homogeneous zircon grains of the highest optical quality. For successful dating experiments on very young and historically well-defined coastal dune sands, selection of the most stable luminescence component by means of narrow band interference filters is needed. Our results suggest that ultimately optical zircon dating will allow us to determine the age of extremely young samples ( e.g. 12 months!).     

Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain

Background

Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon.

Methods

For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants.

Results

We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression.

Conclusions

We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function.     

Chiral Aggregates of Triphenylamine‐Based Dyes for Depleting the Production of Hydrogen Peroxide in the Photochemical Water‐Splitting Process

Recent studies on water‐splitting photoelectrochemical cells (PECs) have demonstrated the intriguing possibility of controlling the spin state in this chemical reaction to form H₂ and O₂ by exploiting the chirality of organic π‐conjugated supramolecular polymers. Although this fascinating phenomenon has been disclosed, the chiral supramolecular materials reported thus far are not optimized for acting as efficient photosensitizer for dye‐sensitized PECs. In this work we report on the design, synthesis, and characterization of chiral supramolecular aggregates based on C₃‐symmetric triphenylamine‐based dyes that are able to both absorb visible light and control the spin state of the process. Variable temperature‐dependent spectroscopic measurements reveal the assembly process of the dyes and confirm the formation of chiral aggregates, both in solution as well as on solid supports. Photoelectrochemical measurements on TiO₂‐based anodes validate the advantage of using chiral supramolecular aggregates as photosensitizer displaying higher photocurrent compared to achiral analogues. Moreover, fluorimetric tests for the quantification of the hydrogen peroxide produced, confirm the possibility of controlling the spin of the reaction exerting spin‐selection with chiral supramolecular polymers. These results represent a further step towards the next‐generation of organic‐based water‐splitting solar cells.     

Selector for structural isomers of neutral molecules

We have selected and spatially separated the two conformers of 3-aminophenol (C(6)H(7)NO) present in a molecular beam. Analogous to the separation of ions based on their mass-to-charge ratios in a quadrupole mass filter, the neutral conformers are separated based on their different mass-to-dipole-moment ratios in an ac electric quadrupole selector. For a given ac frequency, the individual conformers experience different focusing forces, resulting in different transmissions through the selector. These experiments demonstrate that conformer-selected samples of large molecules can be prepared, offering new possibilities for the study of gas-phase biomolecules.