Der (2-Phenyl-2-trimethylsilyl)ethyl(PTMSEL)-Linker - ein neuer, mit Fluorid spaltbarer Anker für die Festphasensynthese von geschützten Peptiden und Glycopeptiden

Cyclic Dinuclear Organotin Cations Stabilized by Bulky Substituents

The syntheses of sterically congested 2,2-bis(diorganochloridostannyl)propane, Me2C(SnClR2)2 (1; R = CH(SiMe3)2), the related salts [cyclo-{Me2C(SnR2)2X}B(ArF)4] (2, X = Cl; 3, X = OAc; 4, X = OH; ArF = 3,5-(CF3)2C6H3), and the four-membered-ring cyclo-{Me2C(SnR2)2O} (5) are reported. The compounds have been characterized by elemental and EDX analyses, 1H, 11B, 13C, 19F, 29Si, and 119Sn NMR and IR spectroscopy, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction analysis.

In toxic demyelination oligodendroglial cell death occurs early and is FAS independent

Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early – but not in later – stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cel…

ChemInform Abstract: (2-Phenyl-2-trimethylsilyl)ethyl (PTMSE) Esters - A Novel Carboxyl Protecting Group.

Neurocognitive impairments in non-deprived smokers-results from a population-based multi-center study on smoking-related behavior

The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never-smoking controls) participated in a population-based case- control design.The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P < 0.001) and cognitive impulsivity (P < 0.006), while verbal episodic memory, verbal fluency, verbal working memory, and…

The P300 event-related potential and smoking--a population-based case-control study.

A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case-control study N=1318 participants (smokers and never-smoking controls) were investigated at 6 German academic inst…

Resolving Binding Events on the Multifunctional Human Serum Albumin

Abstract Physiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding‐ and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X‐ray crystallography and time‐resolved dyn…

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Abstract Background Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results wer…

Psychological and hormonal features of smokers at risk to gain weight after smoking cessation--results of a multicenter study.

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with …

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. &lt;b&gt;&lt;i&gt;Method:&lt;/i&gt;&lt;/b&gt; We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a pop…

Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample.

Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected …

The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL)-linker in the synthesis of glycopeptide partial structures of complex cell surface glycoproteins.

The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL) linker represents a novel fluoride-sensitive anchor for the solid-phase synthesis of protected peptides and glycopeptides. Its cleavage is achieved under almost neutral conditions using tetrabutylammonium fluoride trihydrate in dichloromethane thus allowing the construction of complex molecules sensitive to basic and acidic media commonly required for the cleavage of standard linker systems. The advantages of the PTMSEL linker are demonstrated in the synthesis of glycopeptides from the liver intestine (LI)-cadherin and the mucin MUC1, bearing carbohydrate moieties such as N-linked chitobiose or O-linked sialyl-T(N)-residues. The synthesis of the…

Status and recent developments at the polarized-electron injector of the superconducting Darmstadt electron linear accelerator S-DALINAC

At the superconducting Darmstadt electron linac a 100 keV source of polarized electrons has been installed. Major components had been tested prior to installation at an offline teststand. Commissioning of the new source at the S-DALINAC will take place early in 2011. We report on the performance of the teststand, simulations, developments on the laser systems, new radio-frequency components for the S-DALINAC injector, and the status of the implementation of the source.

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After t…

The German multi-centre study on smoking-related behavior-description of a population-based case-control study

Tobacco smoking is a major risk factor for most of the diseases leading in mortality. Nicotine dependence (ND), which sustains regular smoking, is now acknowledged to be under substantial genetic control with some environmental contribution. At present, however, genetic studies on ND are mostly conducted in populations that have been poorly characterized with regard to ND-related phenotypes for the simple reason that the respective populations were not primarily collected to study ND. The German multi-centre study 'Genetics of Nicotine Dependence and Neurobiological Phenotypes', which is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Priority …

The (2-Phenyl-2-trimethylsilyl)ethyl(PTMSEL) Linker—A Novel Linker for the Solid-Phase Synthesis of Protected Peptides and Glycopeptides Cleavable with Fluoride This work was supported by the Volkswagen-Stiftung and by the Fonds der Chemischen Industrie. M.W. is grateful for a fellowship of the Boehringer-Ingelheim-Stiftung.

Flux-flow instability and heating effects in Bi2Sr2CaCu2O8 and YBa2Cu3O7 thin films

Abstract We investigated current–voltage curves of Bi 2 Sr 2 CaCu 2 O 8 and YBa 2 Cu 3 O 7 thin films. Voltage jumps due to flux-flow instabilities at high vortex-velocities were found and interpreted in the framework of the theory of Larkin and Ovchinnikov. The extensions introduced by Bezuglyj et al. account for quasiparticle heating during the measurement. While in Bi 2 Sr 2 CaCu 2 O 8 the instability is found in the vortex-liquid phase, in YBa 2 Cu 3 O 7 we observed it in the vortex-glass phase. Moreover, we studied the temporal behavior of the instability in current–voltage curves with a time resolution in the microsecond range.

Impaired sleep quality and sleep duration in smokers-results from the German Multicenter Study on Nicotine Dependence

Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nicotine dependence. Therefore, determining the frequency of sleep disturbance in otherwise healthy smokers and its association with degree of nicotine dependence is highly relevant. In a population-based case-control study, 1071 smokers and 1243 non- smokers without lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorder were investigated. S…

P50 sensory gating and smoking in the general population

P50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking-related characteristics. In this multicenter study at six academic institutions throughout Germany, n = 907 never-smokers (NS < 20 cigarettes/lifetime), n = 463 light smokers (LS) with Fagerstrom Test for Nicotine Dependence (FTND) ≥ 4 and n = 353 heavy smokers (HS, FTND < 4) were randomly selected from the gene…

Schiff-Base Podates – X-ray, NMR and Ab Initio Molecular-Orbital Studies of the Cadmium(II) Complexes of Linear and Three-Armed Podands in Solution and Solid State

Cadmium(II) complexes of two Schiff bases, 1,3-di(pyridine-2-carboxaldimino)propane (C15H16N4, L1)[1] and tris[4-(2′-pyridyl)-3-aza-3-butenyl]amine (C24H27N7, L2)[2] are described. An efficient route utilising molecular sieves for the synthesis of Schiff bases is presented. The ligands L1 and L2 can be described as linear and three-armed podands, respectively, L1 being conformationally flexible and L2 preorganised. Cadmium perchlorate in methanol with L1 yields a crystalline complex [Cd(L1)2](ClO4)2 (1), the structure of which was determined by X-ray structure analysis. The complex 1 has an unusual nonsymmetrical 8-coordinated helical structure and crystallizes in an acentric space group (C…

Lack of association of a functional catechol-O-methyltransferase gene polymorphism with risk of tobacco smoking: results from a multicenter case-control study

Background The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. Methods In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 cur…

Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large Population-Based Sample

PLoS one 11(4), e0152984 (2016). doi:10.1371/journal.pone.0152984

ChemInform Abstract: The (2-Phenyl-2-trimethylsilyl)ethoxycarbonyl (Psoc) Group - A Novel Amino Protecting Group.

Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls

Abstract Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. So far, the published studies of nicotine effects on antisaccade performance in schizophrenia patients only tested participants who were deprived smokers. Thus, we aimed to test both smoking and non-smoking patients as well as healthy controls in order to extend previous findings. Moreover, we employed a paradigm using standard and delayed trials. We hypothesized that, if nicotine is a genuine cognitive enhancer, its administration would improve antisaccade performance both in smoking and non-smoking participants. A total of 22 patients with schizophrenia (12 smokers and 10 non-smokers) a…

Der (2-Phenyl-2-trimethylsilyl)ethyl-(PTMSE)-Ester – eine neutral spaltbare Carboxyschutzgruppe/The (2-Phenyl-2-trimethylsiylyl)ethyl (PTMSE) Ester – a Carboxy Protecting Group Cleavable under Neutral Conditions

(2-Phenyl-2-trimethylsilyl)ethyl (PTMSE) esters of aminoacids and peptides are stable under the conditions of hydrogenolytic cleavage of benzoxycarbonyl(Z) and benzyl ester groups, base-induced removal of Fmoc groups, palladium(0)-catalyzed removal of allyloxycarbonyl (Aloc) and even acidolytic cleavage of Boc groups. PTMSE esters are also stable under the conditions of peptide condensation reactions. The PTMSE ester is selectively cleaved by treatment with tetrabutylammonium fluoride (TBAF) trihydrate in dichloromethane, i. e. under almost neutral conditions, within a few minutes and, therefore, considered a valuable novel carboxy protecting group.

CCDC 1409484: Experimental Crystal Structure Determination

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CCDC 1409486: Experimental Crystal Structure Determination

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CCDC 1917091: Experimental Crystal Structure Determination

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CCDC 1409487: Experimental Crystal Structure Determination

Related Article: Michael Wagner, Bernhard Zobel, Christina Dietz, Dieter Schollmeyer, and Klaus Jurkschat|2015|Organometallics|34|5602|doi:10.1021/acs.organomet.5b00829

CCDC 1409488: Experimental Crystal Structure Determination

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CCDC 1409485: Experimental Crystal Structure Determination

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