The cell-penetrating peptide TAT(48-60) induces a non-lamellar phase in DMPC membranes.

Cell-penetrating peptides (CPPs) are short polycationic sequences that can translocate into cells without disintegrating the plasma membrane. CPPs are useful tools for delivering cargo, but their molecular mechanism of crossing the lipid bilayer remains unclear. Here we study the interaction of the HIV-derived CPP TAT (48-60) with model membranes by solid-state NMR spectroscopy and electron microscopy. The peptide induces a pronounced isotropic (31)P NMR signal in zwitterionic DMPC, but not in anionic DMPG bilayers. Octaarginine and to a lesser extent octalysine have the same effect, in contrast to other cationic amphiphilic membrane-active peptides. The observed non-lamellar lipid morphology is attributed to specific interactions of polycationic peptides with phosphocholine head groups, rather than to electrostatic interactions. Freeze-fracture electron microscopy indicates that TAT(48-60) induces the formation of rodlike, presumably inverted micelles in DMPC, which may represent intermediates during the translocation across eukaryotic membranes.     

The Carbenic Insertion into the P-P Bond

Abstract

The cycloaddition reactions on Phosphorus Chemistry¹ has allowed a new development of the three membered ring organophosphorus compounds. Starting from functionulized diphosphiranes obtained by action of carbenes on diphosphenes, we have studied their ring opening reactions leading to carbon insertion into P-P bond.     

Role and Perspective of Molecular Simulation-Based Investigation of RNA–Ligand Interaction: From Small Molecules and Peptides to Photoswitchable RNA Binding

Aberrant RNA–protein complexes are formed in a variety of diseases. Identifying the ligands that interfere with their formation is a valuable therapeutic strategy. Molecular simulation, validated against experimental data, has recently emerged as a powerful tool to predict both the pose and energetics of such ligands. Thus, the use of molecular simulation may provide insight into aberrant molecular interactions in diseases and, from a drug design perspective, may allow for the employment of less wet lab resources than traditional in vitro compound screening approaches. With regard to basic research questions, molecular simulation can support the understanding of the exact molecular interaction and binding mode. Here, we focus on examples targeting RNA–protein complexes in neurodegenerative diseases and viral infections. These examples illustrate that the strategy is rather general and could be applied to different pharmacologically relevant approaches. We close this study by outlining one of these approaches, namely the light-controllable association of small molecules with RNA, as an emerging approach in RNA-targeting therapy.     

Structural determination by atmospheric pressure photoionization tandem mass spectrometry of some compounds isolated from the SARA fractions obtained from bitumen

We have identified compounds obtained from the SARA fractions of bitumen by using atmospheric pressure photoionization mass spectrometry and low‐energy collision tandem mass spectrometric analyses with a QqToF‐MS/MS hybrid instrument. The identified compounds were isolated from the maltene saturated oil and the aromatic fractions of the SARA components of a bitumen. The QqToF instrument had sufficient mass resolution to provide accurate molecular weight information and to enhance the tandem mass spectrometry results. The APPI‐QqToF‐MS analysis of the separated compounds showed a series of protonated molecules [M + H]⁺ and molecular ions [M]^+? of the same mass but having different chemical structures, in the maltene saturated oil and the aromatic SARA fractions. These isobaric ions were a molecular ion [M₂]^+? at m/z 418.2787 and a protonated molecule [M₅ + H]⁺ at m/z 287.1625 in the saturated oil fraction, and molecular ions [M₆]^+? at m/z 418.1584 and [M₇]^+? at m/z 287.1285 in the aromatic fraction. The identification of this series of chemical compounds was achieved by performing CID‐MS/MS analyses of the molecular ions [M]^+? ([M₁]^+? at m/z 446. 2980, [M₂]^+? at m/z 418.2787, [M₃]^+? at m/z 360.3350 and [M₄]^+? at m/z 346.2095) in the saturated oil fraction and of the [M₅ + H]⁺ ion at m/z 287.1625 also in the saturated oil fraction. The observed CID‐MS/MS fragmentation differences were explained by proposed different breakdown processes of the precursor ions. The presented tandem mass spectrometric study shows the capability of MS/MS experiments to differentiate between different classes of chemical compounds of the SARA components of bitumen and to explain the reasons for the observed mass spectrometric differences. However, greater mass resolution than that provided by the QqToF‐MS/MS instrument would be required for the analysis of the asphaltene fraction of bitumen. Copyright © 2011 John Wiley & Sons, Ltd.     

Magnetic microstructure of nanocrystalline FeCuNbSiB soft magnets

The soft magnetic properties and the domain patterns of optimized nanocrystalline FeCuNbSiB-alloys are typically comparable to those of highly permeable Co-based amorphous alloys. Yet the nanocrystalline alloys show some specific peculiarities absent in the amorphous case. The most prominent example is patchy magnetization patterns which reflect the residual contribution of the averaged random magneto-crystalline anisotropy to the magnetization process. The article surveys the typical characteristics and the consequences for the magnetization process.     

Organic semiconductors for solution-processable field-effect transistors (OFETs)

The cost-effective production of flexible electronic components will profit considerably from the development of solution-processable, organic semiconductor materials. Particular attention is focused on soluble semiconductors for organic field-effect transistors (OFETs). The hitherto differentiation between "small molecules" and polymeric materials no longer plays a role, rather more the ability to process materials from solution to homogeneous semiconducting films with optimal electronic properties (high charge-carrier mobility, low threshold voltage, high on/off ratio) is pivotal. Key classes of materials for this purpose are soluble oligoacenes, soluble oligo- and polythiophenes and their respective copolymers, and oligo- and polytriarylamines. In this context, micro- or nanocrystalline materials have the general advantage of somewhat higher charge-carrier mobilities, which, however, could be offset in the case of amorphous, glassy materials by simpler and more reproducible processing.     

Comparison of solid-phase extraction sorbents for sample clean-up in the analysis of organic explosives

In this study, a method was developed for determination of steroid hormones (17beta-estradiol, estrone, 17alpha-ethynylestradiol) in tap and sewage water samples from Sweden. Sample preparation and analysis were performed by a hollow-fibre microporous membrane liquid-liquid extraction (HF-MMLLE) set-up combined with gas chromatography-mass spectrometry (GC-MS). In this approach, only the organic liquid in the lumen (10microL) of the hollow-fibre membrane was utilised for depleting extraction. Several parameters were studied, including: type of organic solvent, sample pH, salt and humic acid content. The optimised method allowed the determination of the analyte at the low ngL(-1) level in tap and sewage water. A linear plot gave correlation coefficients better than 0.995 and resulted in a method limit of detection of 1.6, 3 and 10ngL(-1) for 17beta-estradiol, estrone, and 17alpha-ethynylestradiol, respectively, in sewage water. Enrichment factors were over 1400 after derivatisation. The repeatabilities at 50 and 600ngL(-1) were better than 10% and 6%, respectively.     

A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for ⁸⁹Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the ⁸⁹Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate ⁸⁹Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for ⁸⁹Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new ⁸⁹Zr-based complex. High stability in vivo, with low accumulation of free ⁸⁹Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final ⁸⁹Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.     

On the stereochemistry of the aldol-addition

NOE-experiments and STO-3G calculations suggest that E-enol borates exist in an U-conformation $\text{7a}$, whereas the Z-enol borates should prefer the extended conformation $\text{8b}$. These observations have been linked to the stereoselectivity of the aldol addition. The resulting predictions are in line with the stereoselectivity observed on addition of cyclohexenol borates to benzaldehyde.