Design, synthesis and evaluation of β-lactam antigenic peptide hybrids; unusual opening of the β-lactam ring in acidic media

β-Lactam peptides were envisioned as conformational constraints in antigenic peptides (APs). Three different β-lactam tripeptides of varying flexibility were prepared in solution and incorporated in place of the central part of the altered melanoma associated antigenic peptide Leu(27)-Melan-A(26-35) using solid phase synthesis techniques. Upon TFA cleavage from the solid support, an unexpected opening of the β-lactam ring occurred with conservation of the amide bond. After adaptation of the solid phase synthesis strategy, β-lactam peptides were successfully obtained and both opened and closed forms were evaluated for their capacity to bind to the antigen-presenting class-I MHC HLA-A2 protein system. None of the closed β-lactam peptides bound to HLA-A2, but their opened variants were shown to be moderate to good HLA-A2 ligands, one of them being even capable of stimulating a Melan-A-specific T cell line.     

Extended characterization of a vacuum gas oil by offline LC‐high‐temperature comprehensive two‐dimensional gas chromatography

In a context of environmental preservation, purification and conversion of heavy petroleum cuts into high‐quality fuel becomes essential. The interest for the characterization of those very complex matrices becomes a trendy analytical challenge, when it comes to get molecular information for the optimization of industrial processes. Among new analytical techniques, high‐temperature 2‐D GC has recently proved its applicability to heavy petroleum matrices, but lacks in selectivity to separate all chemical groups. To gain resolution, heart cutting is demonstrated for LC separation of saturated, aromatic and polar compounds prior to high‐temperature 2‐D GC. Therefore, an extended global resolution was obtained, especially by a better distinction of saturated compounds. This includes iso‐paraffins and biomarker polynaphthenic structures, which are impossible to quantify with MS methods. This new way to analyze heavy petroleum fractions gives innovative opportunities for the construction of global weight distributions by carbon atoms number and by chemical families. This can right now be employed for quantitative analysis of heavy petroleum fractions and for studying conversion processes.     

Functionalization and Application of Cellulose Microparticles as Adsorbents in Extracorporeal Blood Purification

Therapeutic apheresis is established as supportive therapy for various diseases, such as hypercholesterolemia, autoimmune diseases, liver failure, and sepsis. In combined membrane-adsorption systems, the patient's plasma is continuously separated from whole blood by means of a hollow fiber filter, and pathogenic factors are removed from the plasma by selective or specific adsorbents. While adsorbent particles with a size range of 300–800 µm are used in conventional systems, we are currently developing a system based on adsorbent microparticles (1–5 µm), the Microspheres-Based Detoxification System (MDS). The characteristics of the matrix used for immobilization of specific ligands influence the performance of the resulting adsorbents. Desirable matrix characteristics are an open porous structure with an inner surface accessible for target molecules, mechanical stability, narrow particle size distribution, and ease of derivatization. In addition, biocompatibility is a critical issue, since the particles are in direct contact with the patient's plasma. Cellulose represents an ideal support matrix, as it combines all the above-mentioned features, and cellulosic polymers are widely applied in medicine and generally regarded as biocompatible. Cellulose microparticles can be activated using e.g. sodium periodate and functionalized with Polymyxin B or anti-tumor necrosis factor (TNF) antibodies to generate specific adsorbents for endotoxins or TNF. In summary, cellulose microparticles represent an excellent matrix as basis for adsorbent development in blood purification.     

Synthesis and Characterization of a Novel Triangular Rh2Au Cluster Compound Inspired by the Isolobality Concept

The synthesis of [Rh₂(η⁵-Cp)₂(μ-H)(μ-PPh₂)₂]BF₄ ( 2 ) by protonation reaction of the metal basic complex [Rh₂(η⁵-Cp)₂(μ-PPh₂)₂] ( 1 ) with tetrafluoroboric acid in diethyl ether is described. Complex salt 2 was obtained in high yield and fully characterized by spectroscopic means and X-ray crystal diffraction. Applying the isolobal analogy between H and the fragment Au(PPh₃) as a synthetic strategy on the reaction of compound 2 with equimolar amounts of [Au(CH₃)(PPh₃)] in refluxing acetone resulted in the formation of the expected triangular cluster compound [Rh₂{μ-Au(PPh₃)}(η⁵-Cp)₂(μ-PPh₂)₂]BF₄ ( 3 ) in good yield. Metal cluster salt 3 was fully characterized by spectroscopic data and its molecular structure in the crystal was determined by X-ray diffraction. The structural comparison of the protonated dirhodium core in the cationic complex of 2 with the Rh₂Au framework in 3 is in good accordance with the isolobal relation between H⁺ and Au⁺ because they share the respective same position in these closely related molecular structures.     

Development and experimental validation of a patient-specific lumbar spine FE model to predict the effects of instrumentations

A lumbar spine model without instrumentations was created using CT data and validated with experimental results of the same specimen. The specimen was loaded with pure moments in a spine test rig. The material parameters were taken from literature and adapted for better simulation of the experiments. The results show that further calibration of the material parameters and the implementation of additional ligamentous structures are necessary to simulate the spine's motion reliably. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Changes in Feed Proanthocyanidin Profiles during Silage Production and Digestion by Lamb

Proanthocyanidins are plant specialized metabolites which are beneficial to animal nutrition and health. This study determined how proanthocyanidin profiles of sainfoin (Onobrychis viciifolia) and birdsfoot trefoil (Lotus corniculatus) change during the forage conservation process and along the digestive tract of lamb. We determined soluble, protein- and fiber-bound proanthocyanidins by spectrophotometric methods and soluble proanthocyanidin profiles by UPLC-MS/MS. During the conservation process, the total proanthocyanidin contents reduced in both forages and the relative proportion of insoluble proanthocyanidins increased, especially in sainfoin. The soluble proanthocyanidins, their mean degree of polymerization and the relative prodelphinidin share declined in both feed species. In the abomasum of lambs fed sainfoin silage, most of the proanthocyanidins were in insoluble form bound to proteins and fibers, but in the small and large intestines, the proportion of soluble proanthocyanidins increased again. For lambs fed birdsfoot trefoil, the trend was not so clear as proanthocyanidins were already mainly soluble in the abomasum. Nevertheless, a large part of soluble proanthocyanidins was recovered in the digestive tract but could not be detected by the UPLC-MS/MS method used. This study suggests that proanthocyanidins have probably been metabolized in the digestive tract by the resident microbiota.     

Reactivity of Cyanide and Thiocyanate Towards the Nitrosyl Carbonyl [Co(CO)3(NO)]

The reaction of equimolar amounts of [Co(CO)₃(NO)] and [PPN]CN, PPN⁺ = (PPh₃)₂N⁺, in THF at room temperature resulted in ligand substitution of a carbonyl towards the cyanido ligand presumably affording the complex salt PPN[Co(CO)₂(NO)(CN)] as a reactive intermediate species which could not be isolated. Applying the synthetic protocol using the nitrosyl carbonyl in excess, the title reaction afforded unexpectedly the novel complex salt PPN[Co₂(μ-CN)(CO)₄(NO)₂] ( 1 ) in high yield. Because of many disorder phenomena in crystals of 1 the corresponding NBu₄⁺ salt of 1 has been prepared and the molecular structure of the dinuclear metal core in NnBu₄[Co₂(μ-CN)(CO)₄(NO)₂] ( 2 ) was determined by X-ray crystal diffraction in a more satisfactory manner. In contrast to the former result, the reaction of [PPN]SCN with [Co(CO)₃(NO)] yielded the mononuclear complex salt PPN[Co(CO)₂(NO)(SCN-κN)] ( 3 ) in good yield whose molecular structure in the solid was even determined and its composition additionally confirmed by spectroscopic means.