Modulating Mucin Hydration and Lubrication by Deglycosylation and Polyethylene Glycol Binding

A key property of mucin glycoproteins is their exceptional capacity to hydrate and lubricate surfaces. In vivo, mucins assemble into mucus hydrogels that cover the epithelium and protect it from dehydration and shear stress. A better understanding of the origin of these properties could lead to new treatment strategies for patients with poor mucus coverage, defective mucus production, or glycosylation as caused by Sjögren syndrome, dry eye, or in the case of certain bacterial infections. In this work, mucin coatings are used to show that mucin‐associated glycans are essential for the formation of such hydrated and lubricating layers. Native mucins are compared with deglycosylated mucins by analyzing their hydration and it is shown that their lubricative potential in the boundary and mixed lubrication regime is linked to the hydration. The removal of glycans from the mucin results in a 3.5‐fold decrease in hydration and an increase in friction by two orders of magnitude. This loss of function is countered by grafting polyethylene glycol (PEG) molecules to defective mucins through lectin–glycan interactions. This lectin‐PEG conjugation restores hydration and improves lubrication of the partially deglycosylated mucin coatings. Thus, local complementation of defective mucus layers could prove to be a useful new treatment strategy.     

A Novel Process for Selective Ruthenium‐Catalyzed Oxidation of Naphthalenes and Phenols

Arenes are selectively oxidized to the corresponding quinones employing ruthenium(2,2′,6′:2′′‐terpyridine)(2,6‐pyridinedicarboxylate) [Ru(tpy)(pydic] as catalyst and hydrogen peroxide as the terminal oxidant. Applying alkylated naphthalenes and phenols, benzo‐ and naphthoquinones are obtained in up to 93% yield. The industrially interesting oxidation of 2‐methylnaphthalene gave 74% of the corresponding quinones and 60% of menadione (vitamin K₃). 2,3,5‐Trimethylbenzoquinone which constitutes the key intermediate for vitamin E is obtained in 83% yield.     

Selective Catalytic Reductions of Amides and Nitriles to Amines

This personal account summarizes our recent developments of catalytic hydrosilylations and hydrogenations of carboxylic amides and nitriles to selectively give amines. Special focus is given to highly chemoselective iron- and zinc-catalyzed reductions of amides.     

N‐Lauroylation during the Expression of Recombinant N‐Myristoylated Proteins: Implications and Solutions

Incorporation of myristic acid onto the N terminus of a protein is a crucial modification that promotes membrane binding and correct localization of important components of signaling pathways. Recombinant expression of N‐myristoylated proteins in Escherichia coli can be achieved by co‐expressing yeast N‐myristoyltransferase and supplementing the growth medium with myristic acid. However, undesired incorporation of the 12‐carbon fatty acid lauric acid can also occur (leading to heterogeneous samples), especially when the available carbon sources are scarce, as it is the case in minimal medium for the expression of isotopically enriched samples. By applying this method to the brain acid soluble protein 1 and the 1–185 N‐terminal region of c‐Src, we show the significant, and protein‐specific, differences in the membrane binding properties of lauroylated and myristoylated forms. We also present a robust strategy for obtaining lauryl‐free samples of myristoylated proteins in both rich and minimal media.     

Ökonomische Bewertung und Optimierung des Automatisierungsgrades von Versicherungsprozessen

In the context of value and customer orientation there are various requirements concerning the process – especially in insurance companies: processes are meant to be standardized, automated, and flexible. It is in question whether a fast and cheap automated processing is preferred to manual handling. For which claims and which process steps is it of economic value to have the flexibility and the competence and ability to solve problems of human operators at your disposal? Various combinations, representing different degrees of automation, are possible. The different degrees of automation for the processing of an insurance claims are compared and resulting cash flows are determined. It is essential to include all consequences that can be attributed to a single process and to consider customer reactions and restrictions to the capacity of processing. Instead of using heuristic rules to decide on automation in practice, here the decision is flexible and depends on the given situation. Viewing an aggregated number of insurance claims it is possible to deduce information about the performance of the process. The model is exemplarily illustrated with help of a part of the process for handling own damage glass claims.     

Genetically Encoded Biotin Analogues: Incorporation and Application in Bacterial and Mammalian Cells

The biotin–streptavidin interaction is among the strongest known in nature. Herein, the site-directed incorporation of biotin and 2-iminobiotin composed of noncanonical amino acids (ncAAs) into proteins is reported. 2-Iminobiotin lysine was employed for protein purification based on the pH-dependent dissociation constant to streptavidin. By using the high-affinity binding of biotin lysine, the bacterial protein RecA could be specifically isolated and its interaction partners analyzed. Furthermore, the biotinylation approach was successfully transferred to mammalian cells. Stringent control over the biotinylation site and the tunable affinity between ncAAs and streptavidin of the different biotin analogues make this approach an attractive tool for protein interaction studies, protein immobilization, and the generation of well-defined protein–drug conjugates.     

New Cav1.2 Channelopathy with High-Functioning Autism,Affective Disorder,Severe Dental Enamel Defects,a Short QT Interval,and a Novel CACNA1C Loss-of-Function Mutation

Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.     

A General Method for the Enantioselective Hydrogenation of β‐Keto Esters using Monodentate Binaphthophosphepine Ligands

17 monodentate phosphepine ligands with a 4,5‐dihydro‐3H‐dinaphtho[2,1‐c;1′,2′‐e]phosphepine structural motif have been synthesized and tested in the asymmetric hydrogenation of various β‐keto esters. By variation of the substituents of the aryl group on the phosphorus atom a fine tuning of the selectivity of the catalytic system is possible. Quantitative yield and enantioselectivities up to 95% ee have been achieved for the hydrogenation of methyl acetoacetate ( 7a ), methyl 3‐oxovalerate ( 7b ) and ethyl 4‐phenyl‐3‐oxo‐propionate ( 7d ) using 4‐(4‐methoxyphenyl)‐4,5‐dihydro‐3H‐dinaphtho‐[2,1‐c;1′,2′‐e]phosphepine ( 4g ) as ligand. Best enantioselectivities were obtained at comparably high temperatures (100–120 °C), which had the advantage of increased reaction rates.