Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I

The structure and biological activities of two disulphide isomersof a C-region deletion mutant of insulin-like growth factor-I(IGF-I) which has an Asn–Gly link engineered at the junctionof the A- and B-regions were studied before and after chemicalcleavage. Circular dichroism (CD) spectra and binding affinityto IGF binding protein 3 (IGFBP3) indicated that the treatmentwith hydroxylamine did not disrupt the overall tertiary foldof the hormones. Cleavage restored some binding affinity forthe IGF-I receptor in both isomers and weakly restored the abilityto stimulate incorporation of tritiated thymidine into DNA inNIH 3T3 fibroblasts transfected with the human IGF-I receptor.Cleavage also restored metabolic capacity, as measured by theability of the isomers to promote lipogenesis in isolated ratadipocytes through the insulin receptor. These results are consistentwith the theory that binding of IGF-I to the IGF-I receptorrequires a conformational change similar to that involved ininsulin binding the insulin receptor. The weak affinity forthe IGF-I receptor after cleavage is consistent with the beliefthat residues in the C-region interact with the IGF-I receptor.This structural difference between insulin and IGF-I gives eacha higher binding affinity for its own receptor.     

Aging effect of atmospheric pressure plasma jet treated polycaprolactone polymer solutions on electrospinning properties

In previous work, an atmospheric pressure plasma jet was applied to successfully improve the electrospinnability of poly-ε-caprolactone (PCL) which enabled the fabrication of beadless nanofibers. In this paper, we report the aging effect of the plasma treatment to evaluate the robustness of the developed process. For this purpose, plasma-treated PCL polymer solutions with different exposure time were stored for 1 and 8 days and the aged solutions were analyzed in terms of conductivity, viscosity, surface tension, pH, and polymer molecular weight. During storage, the surface tension and acidity of the plasma-treated solutions were maintained constant. However, the viscosity was found to be significantly lower after 8 days which was attributed to PCL degradation. Electrospinning of all stored PCL solutions resulted in the generation of beadless PCL nanofibers. The plasma treatment effects were thus found to be highly stable over time and capable of producing high-quality PCL nanofibers up to 8 days. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48914.     

Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16

The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α₂β₂ and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (K_i=4.9 μM) of the lead compound (+)- 3 a (K_i=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α₂β₂ holoenzyme, the CK2α subunit or the mutated CK2α′ ^C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (K_i=3.6 μM) and the N-methylimide (+)- 10 a (K_i=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (K_i=1.8 μM) of this series of compounds.     

Wachstumsmessungen von Kristallen in sauberen und verunreinigten Lösungen: Einzelkristall vs. Kollektiv

Information about crystal growth rates and the influence of impurities are essential for the design of industrial crystallization processes. Here, the influence of trivalent metal ions Fe³⁺ in solution and adsorbed in the crystal on the growth and dissolution rate is investigated. The results clearly show kinetic and thermodynamic effects caused by impurities which have to be taken into account in the equipment design. Furthermore, effects of growth rate dispersion must be excluded by investigation of crystal collectives. Additionally, the crystal growth data should be obtained from real starting solutions.     

Thermal and Electrical Conductivity of Amorphous and Graphitized Carbide‐Derived Carbon Monoliths

The influence of graphitization and composition of carbide‐derived carbon (CDC) monoliths on the electrical and thermal conductivity was investigated. Carbon monoliths with varying porosities were synthesized employing biomorphous macroporous TiC and SiC as precursors. Graphitization was carried out in situ during high‐temperature chlorination with and without addition of nickel, iron, and cobalt chloride to the carbide. The graphitized monoliths showed improved properties. The results demonstrate that despite graphitic carbon also glass‐like carbon, stemming from the carbide synthesis, increases the thermal and electrical conductivity significantly.     

Ketonization of Proline Residues in the Peptide Chains of Actinomycins by a 4‐Oxoproline Synthase

X‐type actinomycins (Acms) contain 4‐hydroxyproline (Acm X₀) or 4‐oxoproline (Acm X₂) in their β‐pentapeptide lactone rings, whereas their α ring contains proline. We demonstrate that these Acms are formed through asymmetric condensation of Acm half molecules (Acm halves) containing proline with 4‐hydroxyproline‐ or 4‐oxoproline‐containing Acm halves. In turn, we show—using an artificial Acm half analogue (PPL 1) with proline in its peptide chain—their conversion into the 4‐hydroxyproline‐ and 4‐oxoproline‐containing Acm halves, PPL 0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus. Two responsible genes of the Acm X biosynthetic gene cluster of S. antibioticus, saacmM and saacmN, encoding a cytochrome P450 monooxygenase (Cyp) and a ferredoxin were identified. After coexpression in Escherichia coli, their gene products converted PPL 1 into PPL 0 and PPL 2 in vivo as well as in situ in permeabilized cell of the transformed E. coli strain in conjunction with the host‐encoded ferredoxin reductase in a NADH (NADPH)‐dependent manner. saAcmM has high sequence similarity to the Cyp107Z (Ema) family of Cyps, which can convert avermectin B1 into its keto derivative, 4′′‐oxoavermectin B1. Determination of the structure of saAcmM reveals high similarity to the Ema structure but with significant differences in residues decorating their active sites, which defines saAcmM and its orthologues as a distinct new family of peptidylprolineketonizing Cyp.     

SkaSim – Skalierbare HPC‐Software für molekulare Simulationen in der chemischen Industrie

This article outlines advances in molecular modeling and simulation using massively parallel high‐performance computers (HPC). In the SkaSim project, partners from the HPC community collaborated with users from science and industry. The aim was to optimize the prediction of thermodynamic property data in terms of efficiency, quality and reliability using HPC methods. In this context, various topics were dealt with: atomistic simulation of homogeneous gas bubble formation, surface tension of classical fluids and ionic liquids, multicriteria optimization of molecular models, the development of the molecular simulation codes ls1 mardyn and ms2, atomistic simulation of gas separation processes, molecular membrane structure generators, transport resistors and the evaluation of predictive property data models based on specific mixture types.     

Blends of Two Perylene Derivatives: Mesogenic Properties and Application As Emitter Materials in OLEDs

Blends consisting of two components, namely a liquid crystalline perylene ester and a bilaterally extended perylene ester, were studied. The liquid crystalline properties of these blends were investigated in detail by means of polarized optical microscopy and differential scanning calorimetry. The resulting phase diagram was used to explore the potential of these blends as emitter layers in OLEDs, which were prepared via thermal evaporation in a vacuum and spin coating of solutions.